Berotralstat, (RS)-

Details

Stereochemistry	RACEMIC
Molecular Formula	C30H26F4N6O
Molecular Weight	562.5607
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NCC1=CC(=CC=C1)N2N=C(C=C2C(=O)NC3=CC(=CC=C3F)C(NCC4CC4)C5=CC=CC(=C5)C#N)C(F)(F)F

InChI

InChIKey=UXNXMBYCBRBRFD-UHFFFAOYSA-N

InChI=1S/C30H26F4N6O/c31-24-10-9-22(28(37-17-18-7-8-18)21-5-1-3-19(11-21)15-35)13-25(24)38-29(41)26-14-27(30(32,33)34)39-40(26)23-6-2-4-20(12-23)16-36/h1-6,9-14,18,28,37H,7-8,16-17,36H2,(H,38,41)

HIDE SMILES / InChI

Molecular Formula	C30H26F4N6O
Molecular Weight	562.5607
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214094s000lbl.pdf|https://pubmed.ncbi.nlm.nih.gov/33646555

Berotralstat (ORLADEYO™; BCX7353) is an orally administered kallikrein inhibitor, which has been developed by BioCryst Pharmaceuticals for hereditary angioedema (HAE). The inhibition of kallikrein by berotralstat decreases the production of bradykinin, which prevents the localised tissue oedema that occurs during attacks of HAE. Berotralstat has been approved in the USA, and subsequently in Japan, for prophylaxis to prevent attacks of HAE in adults and paediatric patients aged 12 years or older.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Plasma kallikrein 9 Target ID: CHEMBL2000 Sources: https://www.ema.europa.eu/en/documents/assessment-report/orladeyo-epar-public-assessment-report_en.pdf\|https://patents.google.com/patent/WO2015134998A1/en	Inhibitor 8504		44.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hereditary angioedema 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214094s000lbl.pdf	Preventive		Approved 8583	ORLADEYO Approved Use Indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. Launch Date 2020

C_max

Value	Dose	Analyte	Population
97.8 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=52	110 mg 1 times / day steady-state, oral dose: 110 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
158 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=52	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
45.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
45.9 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
80.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
57.9 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
68.3 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
89 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=64	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
130 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=64	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1600 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=52	110 mg 1 times / day steady-state, oral dose: 110 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2770 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=52	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
907 ng × h/L OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
945 ng × h/L OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1620 ng × h/L OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
850 ng × h/L OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1250 ng × h/L OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=62	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2063 ng × h/L OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=64	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2252 ng × h/L OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=64	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEROTRALSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
93 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=52	single, oral		BEROTRALSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=52 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=56	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		BEROTRALSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	Disc. AE: Alanine aminotransferase increased, Aspartate aminotransferase increased... AEs leading to discontinuation/dose reduction: Alanine aminotransferase increased (2.4%) Aspartate aminotransferase increased (0.8%) Hepatic enzyme test increased (0.8%) Liver function test abnormal (0.8%) Abdominal pain upper (0.8%) Vomiting (1.6%) Diarrhea (0.8%) Nausea (0.8%) Any other adverse events (3.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT,ADULT Health Status: unhealthy Age Group: ADOLESCENT,ADULT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	Disc. AE: Laboratory abnormality or Adverse event... AEs leading to discontinuation/dose reduction: Laboratory abnormality or Adverse event (2.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	Disc. AE: Laoratory abnormality or Adverse event, Gastrointestinal abdominal adverse event... AEs leading to discontinuation/dose reduction: Laoratory abnormality or Adverse event (7.3%) Gastrointestinal abdominal adverse event (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	Disc. AE: Alanine aminotransferase increased, Aspartate aminotransferase increased... AEs leading to discontinuation/dose reduction: Alanine aminotransferase increased (1%) Aspartate aminotransferase increased (1%) Hepatic enzyme increased (1%) Liver function test abnormal (1%) Abdominal pain upper (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 P-gp 1741 BCRP 910 OATP2B1 157 OCT2 779 MATE1 415 OAT1 725 MATE2-K 77 OATP1B3 961 MRP2 499 OATP1A2 43 OATP1B1 1079 OAT3 747	BCRP 697 OAT3 391 OATP1B3 435 OATP1B1 503 P-gp 2052 MATE1 182 OAT1 395 MATE2-K 33 OCT2 434

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68	moderate [IC50 2.3 uM]	yes (co-administration study) Comment: Following administration of berotralstat 150 mg QD, the Cmax and AUC of dextromethorphan were increased by 196% and 178% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68	moderate [IC50 2.5 uM]	yes (co-administration study) Comment: Following administration of berotralstat 150 mg QD, the Cmax and AUC of midazolam were increased by 45% and 124% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68	no [IC50 12 uM]	yes (co-administration study) Comment: Following administration of berotralstat 300 mg QD, the Cmax and AUC of rosuvastatin were decreased by approximately 20% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	no [IC50 >100 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	no [IC50 >30 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	no [IC50 >30 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	no [IC50 >30 uM]
OATP2B1 162	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	no [IC50 >30 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68	weak [IC50 0.24 uM]	yes (co-administration study) Comment: Following administration of berotralstat 150 mg QD, the Cmax and AUC of tolbutamide were increased by 19% and 73% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68	weak	yes (co-administration study) Comment: Following administration of berotralstat 150 mg QD, the Cmax and AUC of omeprazole were increased by 21% and 24% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68	yes [IC50 0.492 uM]	yes (co-administration study) Comment: Following administration of berotralstat 300 mg QD, the Cmax and AUC of digoxin were increased by 58% and 48%, Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 53 \| 67 \| 68
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	yes [IC50 13.2 uM]
OATP1A2 43	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	yes [IC50 13.3 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	yes [IC50 13.3 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	yes [IC50 3.53 uM]
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=67 Page: 67.0	yes [IC50 4.6 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=66 Page: 66.0	no
MATE2-K 33	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=66 Page: 66.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=66 Page: 66.0	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=66 Page: 66.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=66 Page: 66.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=66 Page: 66.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=66 Page: 66.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=52 Page: 52.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=52 Page: 52.0	yes
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=68 Page: 53 \| 66 \| 68	yes	yes (co-administration study) Comment: Cyclosporine increased Cmax and AUC by 25% and 69% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=68 Page: 53 \| 66 \| 68
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=68 Page: 53 \| 66 \| 68	yes	yes (co-administration study) Comment: Cyclosporine increased Cmax and AUC by 25% and 69% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=53 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=68 Page: 53 \| 66 \| 68

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf#page=30 Page: 30.0

PubMed

Title	Date	PubMed
Orladeyo (Berotralstat): A Novel Oral Therapy for the Prevention of Hereditary Angioedema.	2022-04	34282650
Berotralstat (Orladeyo) for prevention of hereditary angioedema.	2021-07-26	34544111
Berotralstat: First Approval.	2021-02	33646555

Patents

Sample Use Guides

In Vivo Use Guide

Recommended Dosage: One capsule (150 mg) taken orally once daily with food.

Route of Administration: Oral

In Vitro Use Guide

In vitro data demonstrate that BCX7353 is a potent inhibitor of purified plasma kallikrein, with a Ki of 44nM (Study BR-7353-001). BCX7353 has also been shown to have acceptable selectivity for plasma kallikrein over other related serine proteases, with an IC50 of 0.88 nM against plasma kallikrein and IC50 ranging from 3967nM (against plasmin) to >50,000nM against other related serine proteases. BCX7353 was also shown to suppress HK/PKK-dependent BK production on human endothelial cells, with an EC50 of 5.56nM.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 19:19:25 GMT 2025` Edited by `admin` on `Wed Apr 02 19:19:25 GMT 2025`
Record UNII	6HPY825YQD
Record Status	`Validated (UNII)`
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Name

Type

Language

1-[3-(Aminomethyl)phenyl]-N-[5-[(3-cyanophenyl)[(cyclopropylmethyl)amino]methyl]-2-fluorophenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Preferred Name

English

Berotralstat, (RS)-

Common Name

English

1H-Pyrazole-5-carboxamide, 1-[3-(aminomethyl)phenyl]-N-[5-[(3-cyanophenyl)[(cyclopropylmethyl)amino]methyl]-2-fluorophenyl]-3-(trifluoromethyl)-

Systematic Name

English

Code System Code Type Description

FDA UNII

6HPY825YQD

Created by admin on Wed Apr 02 19:19:25 GMT 2025 , Edited by admin on Wed Apr 02 19:19:25 GMT 2025

PRIMARY

PUBCHEM

118355809

Created by admin on Wed Apr 02 19:19:25 GMT 2025 , Edited by admin on Wed Apr 02 19:19:25 GMT 2025

PRIMARY

CAS

1809010-16-9

Created by admin on Wed Apr 02 19:19:25 GMT 2025 , Edited by admin on Wed Apr 02 19:19:25 GMT 2025

PRIMARY

Related Record Type Details


					8YE5ABM3A9

Berotralstat, (S)-

ENANTIOMER -> RACEMATE

Amount:


					XZA0KB1BDQ

Berotralstat

ENANTIOMER -> RACEMATE

Amount:

AE	Significance	Dose	Population
Abdominal pain upper	0.8% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Aspartate aminotransferase increased	0.8% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Diarrhea	0.8% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Hepatic enzyme test increased	0.8% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Liver function test abnormal	0.8% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Nausea	0.8% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Vomiting	1.6% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Alanine aminotransferase increased	2.4% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Any other adverse events	3.2% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT Health Status: unhealthy Age Group: ADOLESCENT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Laboratory abnormality or Adverse event	2.5% Disc. AE	150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT,ADULT Health Status: unhealthy Age Group: ADOLESCENT,ADULT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Gastrointestinal abdominal adverse event	1% Disc. AE	110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Laoratory abnormality or Adverse event	7.3% Disc. AE	110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Alanine aminotransferase increased	1% Disc. AE	110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Aspartate aminotransferase increased	1% Disc. AE	110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Hepatic enzyme increased	1% Disc. AE	110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Liver function test abnormal	1% Disc. AE	110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf
Abdominal pain upper	2% Disc. AE	110 mg 1 times / day multiple, oral Studied dose Dose: 110 mg, 1 times / day Route: oral Route: multiple Dose: 110 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000MultidisciplineR.pdf

Details

SMILES

InChI

DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214094s000lbl.pdf|https://pubmed.ncbi.nlm.nih.gov/33646555

CNS Activity

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214094s000lbl.pdf|https://pubmed.ncbi.nlm.nih.gov/33646555

C_max

T_1/2

F_unbound

Drug as perpetrator