OLMUTINIB HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H26N6O2S.2ClH
Molecular Weight	559.511
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.CN1CCN(CC1)C2=CC=C(NC3=NC4=C(SC=C4)C(OC5=CC(NC(=O)C=C)=CC=C5)=N3)C=C2

InChI

InChIKey=KIHHNWDWKMJZHH-UHFFFAOYSA-N

InChI=1S/C26H26N6O2S.2ClH/c1-3-23(33)27-19-5-4-6-21(17-19)34-25-24-22(11-16-35-24)29-26(30-25)28-18-7-9-20(10-8-18)32-14-12-31(2)13-15-32;;/h3-11,16-17H,1,12-15H2,2H3,(H,27,33)(H,28,29,30);2*1H

HIDE SMILES / InChI

Molecular Formula	C26H26N6O2S
Molecular Weight	486.589
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27357069
Curator's Comment: The description was created based on several sources, including https://www.drugbank.ca/drugs/DB13164 | https://clinicaltrials.gov/ct2/show/record/NCT02485652 | https://www.google.com/patents/WO2011162515A3

Olmutinib is a novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor, used in the treatment of T790M mutation positive non-small cell lung cancer. Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. EGFRs are frequently over-expressed in lung cancer and contribute to activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways which both promote cell survival and proliferation. By inhibiting EGFR activation, Olmutinib attenuates the activation of these tumor-promoting pathways. In the first phase I/II clinical study of Osimertinib, 800 mg/ day was chosen as the dose for subsequent studies, and the dose-limiting toxicity and maximum tolerated dose was not reached. Olmutinib received breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Epidermal growth factor receptor 49 Target ID: CHEMBL2363049 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26968253	Inhibitor 8504		10.0 nM [IC50]
Tyrosine-protein kinase BTK 24 Target ID: CHEMBL5251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27210433	Inhibitor 8504		1.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non-small cell lung cancer 211 Sources: https://clinicaltrials.gov/ct2/show/NCT02444819	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
441.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
931 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1089.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1322.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
910.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1396.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
982.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1495.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
941.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1327.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
267 ng/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
845 ng/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
932 ng/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1226 ng/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2565 ng/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2043 ng/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2432 ng/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
3889.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9383.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10792.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12766.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
8452.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13024.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7483.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13882.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8439.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12566.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3574 ng × h/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9105 ng × h/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
12322 ng × h/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
15537 ng × h/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
36618 ng × h/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
28339 ng × h/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
42198 ng × h/mL EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.3 h EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8.2 h EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9 h EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8.6 h EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.4 h EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8.6 h EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11.3 h EXPERIMENT https://web.archive.org/web/20161008111107/https://www.hanmipharm.com/ehanmi/img/rnd/2013_WCLC_(HM61713).pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLMUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31125491/	unknown, dental		OLMUTINIB plasma	Homo sapiens

Doses

Dose	Population	Adverse events
1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31447004/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31447004/	DLT: abdominal pain, diarrhea... Dose limiting toxicities: abdominal pain (grade 3, 2 patients) diarrhea (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/31447004/
800 mg 1 times / day multiple, oral MTD Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31447004/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31447004/	Other AEs: Diarrhea, Diarrhea... Other AEs: Diarrhea (all grades, 101 patient) Diarrhea (grade 3-4, 4 patients) Pruritus (all grades, 75 patients) Pruritus (grade 3-4, 1 pt) Rash (all grades, 96 patients) Rash (grade 3-4, 10 patients) Nausea (all grades, 77 patients) Nausea (grade 3-4, 3 patients) Decreased appetite (all grades, 67 patients) Decreased appetite (grade 3-4, 1 pt) Palmar-plantar erythrodysesthesia syndrome (all grades, 61 patient) Palmar-plantar erythrodysesthesia syndrome (grade 3-4, 5 patients) Dry skin (all grades, 46 patients) Dry skin (grade 3-4, 1 pt) Skin exfoliation (all grades, 71 patient) Skin exfoliation (grade 3-4, 4 patients) Constipation (all grades, 26 patients) Vomiting (all grades, 38 patients) Vomiting (grade 3-4, 3 patients) Abdominal pain (all grades, 25 patients) Abdominal pain (grade 3-4, 3 patients) Upper abdominal pain (all grades, 32 patients) Upper abdominal pain (grade 3-4, 1 pt) ALT increased (all grades, 40 patients) ALT increased (grade 3-4, 8 patients) Hyperkeratosis (all grades, 32 patients) Hyperkeratosis (grade 3-4, 1 pt) AST increased (all grades, 35 patients) AST increased (grade 3-4, 6 patients) Fatigue (all grades, 27 patients) Fatigue (grade 3-4, 3 patients) Skin hyperpigmentation (all grades, 19 patients) Dyspepsia (all grades, 24 patients) Nail disorder (all grades, 17 patients) Platelet count decreased (all grades, 24 patients) Platelet count decreased (grade 3-4, 1 pt) Pyrexia (all grades, 16 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/31447004/
800 mg 1 times / day multiple, oral Studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33434335/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/33434335/	Disc. AE: epidermal necrolysis... Other AEs: Diarrhea, Diarrhea... AEs leading to discontinuation/dose reduction: epidermal necrolysis (grade 5, 1 pt) Other AEs: Diarrhea (all grades, 62 patients) Diarrhea (grade 3-4, 5 patients) Nausea (all grades, 44 patients) Nausea (grade 3-4, 1 pt) Hyperkeratosis (all grades, 43 patients) Hyperkeratosis (grade 3-4, 4 patients) Rash (all grades, 43 patients) Rash (grade 3-4, 7 patients) Skin exfoliation (all grades, 38 patients) Skin exfoliation (grade 3-4, 1 pt) Vomiting (all grades, 37 patients) Vomiting (grade 3-4, 3 patients) Palmar-plantar erythrodysesthesia syndrome (all grades, 35 patients) Palmar-plantar erythrodysesthesia syndrome (grade 3-4, 7 patients) Increased alanine aminotransferase (all grades, 33 patients) Increased alanine aminotransferase (grade 3-4, 5 patients) interstitial lung disease (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/33434335/

AEs

PubMed

Title	Date	PubMed
Structure-based discovery of novel 4,5,6-trisubstituted pyrimidines as potent covalent Bruton's tyrosine kinase inhibitors.	2016-07-01	27210433

Patents

Sample Use Guides

In Vivo Use Guide

800 mg QD (2 x 400 mg tablets) continuously in 21-day cycles

Route of Administration: Oral

In Vitro Use Guide

Olmutinib was evaluated with the BTK kinase inhibition using Z'-LYTE™ fluorescence resonance energy transfer (FRET) method and ibrutinib was used as the reference compounds. The Z'-LYTE™ biochemical assay employs a FRET-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophores-one at each end-that make up a FRET pair. In the primary reaction (the Kinase Reaction), the kinase transfers the g-phosphate of ATP to a single serine or threonine residue in the synthetic peptide substrate. In the secondary reaction (the Development Reaction), a site-specific protease (the Development Reagent) recognizes and cleaves nonphosphorylated peptides. Phosphorylated peptides exhibit suppressed cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the peptide, whereas uncleaved, phosphorylated peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:19:54 GMT 2025` Edited by `admin` on `Mon Mar 31 22:19:54 GMT 2025`
Record UNII	XY9T35CX4I
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BI-1482694 DIHYDROCHLORIDE

Preferred Name

English

OLMUTINIB HYDROCHLORIDE

Official Name

English

OLMUTINIB HYDROCHLORIDE [USAN]

Common Name

English

OLMUTINIB DIHYDROCHLORIDE

Common Name

English

2-PROPENAMIDE, N-(3-((2-((4-(4-METHYL-1-PIPERAZINYL)PHENYL)AMINO)THIENO(3,2-D)PYRIMIDIN-4-YL)OXY)PHENYL)-, HYDROCHLORIDE (1:2)

Systematic Name

English

N-[3-({2-[4-(4-Methylpiperazin-1-yl)anilino]thieno[3,2-d]pyrimidin-4-yl}oxy)phenyl]prop-2-enamide dihydrochloride

Systematic Name

English

Olmutinib hydrochloride [WHO-DD]

Common Name

English

Code System Code Type Description

SMS_ID

100000177732