PACRITINIB HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H32N4O3.ClH
Molecular Weight	509.04
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.C(CN1CCCC1)OC2=CC=C3C=C2COC\C=C\COCC4=CC(=CC=C4)C5=CC=NC(N5)=N3

InChI

InChIKey=BCWCXLSAGITLKT-BJILWQEISA-N

InChI=1S/C28H32N4O3.ClH/c1-2-13-32(12-1)14-17-35-27-9-8-25-19-24(27)21-34-16-4-3-15-33-20-22-6-5-7-23(18-22)26-10-11-29-28(30-25)31-26;/h3-11,18-19H,1-2,12-17,20-21H2,(H,29,30,31);1H/b4-3+;

HIDE SMILES / InChI

Molecular Formula	C28H32N4O3
Molecular Weight	472.5787
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: http://www.ctibiopharma.com/pipeline/pacritinib/
Curator's Comment: Description was created based on several sources, including http://www.pmlive.com/pharma_news/baxter_licenses_cancer_drug_from_cti_in_$172m_deal_519143 https://www.drugs.com/history/pacritinib.html

Pacritinib (SB1518), discovered in Singapore at the labs of S*BIO Pte Ltd., is an oral tyrosine kinase inhibitor (TKI) with activity against two important activating mutations: Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development as well as inflammatory cytokine expression and immune responses. Activating mutations of JAK2 are implicated in certain blood-related cancers, including myeloproliferative neoplasms (MPNs), leukemia and certain solid tumors. FLT3 is a gene commonly found mutated in patients with acute myeloid leukemia (AML). Pacritinib has demonstrated encouraging results in Phase 1 and 2 studies for patients with myelofibrosis and may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anemia than has been seen in currently approved and in-development JAK inhibitors. Pacritinib is acquired by Cell Therapeutics, Inc. (CTI) and Baxter international and could effectively address an unmet medical need for patients living with myelofibrosis who face treatment-emergent thrombocytopenia on marketed JAK inhibitors. Currently Pacritinib is undergoing preregistration for myelofibrosis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase JAK2 59 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21691275	Inhibitor 8504		23.0 nM [IC50]
Tyrosine-protein kinase receptor FLT3 42 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21691275	Inhibitor 8504		22.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Myelofibrosis 15 Sources: https://clinicaltrials.gov/ct2/show/NCT02055781	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25600203	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		PACRITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.2 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27931243 \| https://www.ctibiopharma.com/wp-content/uploads/pac_eha2_june2013.pdf	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PACRITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
29 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25600203	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		PACRITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
161.3 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27931243 \| https://www.ctibiopharma.com/wp-content/uploads/pac_eha2_june2013.pdf	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PACRITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
25 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25600203	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		PACRITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

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

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 OAT3 747 CYP1A 70 P-gp 1741	P-gp 2052 OAT3 391	CYP1A2 832 CYP3A 142

Drug as perpetrator

Target	Modality	Activity
CYP1A 122	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21604762/	no [IC50 >5 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21604762/	no [IC50 >5 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21604762/	no [IC50 >5 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21604762/	no [IC50 >5 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21604762/	no [IC50 >5 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363679157	yes [IC50 4.6109 uM]
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33523504/	yes [Inhibition 10 uM]
CYP1A2 2333	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/25600203/	yes
CYP3A 317	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/25600203/	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25600203/	major
OAT3 391	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33523504/	no
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21604762/	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003AKX	https://www.1pchem.com/search?query=1P003AKX
AbovChem LLC	HY-16379	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-16379
Angene	AGN-PC-0WH9NM	http://www.angenechemical.com/productshow/AGN-PC-0WH9NM.html
AstaTech	40039	http://astatechinc.com/CPSResult.php?CRNO=40039
Cayman Chemical	16709	http://www.caymanchem.com/app/template/Product.vm/catalog/16709
ChemShuttle	111883	https://www.chemshuttle.com/catalogsearch/result/?q=111883
eMolecules	49383504	https://orderbb.emolecules.com/search/#?query=49383504
eMolecules	50278834	https://orderbb.emolecules.com/search/#?query=50278834
eMolecules	50284860	https://orderbb.emolecules.com/search/#?query=50284860
Matrix Scientific	147225	http://www.matrixscientific.com/147225.html
MolPort	MolPort-039-139-323	https://www.molport.com/shop/molecule-link/MolPort-039-139-323
Selleck Chemicals	S8057	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8057
ShangHai Biochempartner	BCP09091	http://www.biochempartner.com/search_BCP09091
TargetMol	T6020	https://www.targetmol.com/search?keyword=T6020

PubMed

Title	Date	PubMed
SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies.	2011-11	21691275
Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma.	2011-07-14	21604762

Patents

Sample Use Guides

In Vivo Use Guide

Pacritinib 400 mg taken orally, once daily Pacritinib 200 mg taken orally, twice daily

Route of Administration: Oral

In Vitro Use Guide

Pacritinib inhibits cell proliferation of FLT3-ITD-harboring cells MV4-11 and primary AML blast cells with IC50s of 47 nM and 0.19-1.3 uM, respectively.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 04:34:17 GMT 2025` Edited by `admin` on `Wed Apr 02 04:34:17 GMT 2025`
Record UNII	XV36F0JG6L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

14,19-DIOXA-5,7,27-TRIAZATETRACYCLO(19.3.1.12,6.18,12)HEPTACOSA-1(25),2,4,6(27),8,10,12(26),16,21,23-DECAENE, 11-(2-(1-PYRROLIDINYL)ETHOXY)-, HYDROCHLORIDE (1:1)

Preferred Name

English

PACRITINIB HYDROCHLORIDE

Common Name

English

PACRITINIB MONOHYDROCHLORIDE

Common Name

English

Code System Code Type Description

NCI_THESAURUS

C185888

Created by admin on Wed Apr 02 04:34:17 GMT 2025 , Edited by admin on Wed Apr 02 04:34:17 GMT 2025

PRIMARY

CAS

1228923-43-0

Created by admin on Wed Apr 02 04:34:17 GMT 2025 , Edited by admin on Wed Apr 02 04:34:17 GMT 2025

NON-SPECIFIC STOICHIOMETRY

FDA UNII

XV36F0JG6L

Created by admin on Wed Apr 02 04:34:17 GMT 2025 , Edited by admin on Wed Apr 02 04:34:17 GMT 2025

PRIMARY

PUBCHEM

67443473

Created by admin on Wed Apr 02 04:34:17 GMT 2025 , Edited by admin on Wed Apr 02 04:34:17 GMT 2025

PRIMARY

Related Record Type Details


					G22N65IL3O

PACRITINIB

PARENT -> SALT/SOLVATE

Amount:

Related Record Type Details


					G22N65IL3O

PACRITINIB

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: http://www.ctibiopharma.com/pipeline/pacritinib/Curator's Comment: Description was created based on several sources, including http://www.pmlive.com/pharma_news/baxter_licenses_cancer_drug_from_cti_in_$172m_deal_519143 https://www.drugs.com/history/pacritinib.html

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://www.ctibiopharma.com/pipeline/pacritinib/
Curator's Comment: Description was created based on several sources, including http://www.pmlive.com/pharma_news/baxter_licenses_cancer_drug_from_cti_in_$172m_deal_519143 https://www.drugs.com/history/pacritinib.html

C_max

T_1/2

Drug as perpetrator