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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 of PACRITINIB HYDROCHLORIDE

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 ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Description
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

Curator's Comment: Pacritinib was found to cross the blood-brain barrier in NOD-SCID mice

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
23.0 nM [IC50]
22.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer









Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
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 Jul 14
SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies.
2011 Nov
Patents

Sample Use Guides

Pacritinib 400 mg taken orally, once daily Pacritinib 200 mg taken orally, twice daily
Route of Administration: Oral
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 Thu Jul 06 20:44:45 UTC 2023
Edited
by admin
on Thu Jul 06 20:44:45 UTC 2023
Record UNII
XV36F0JG6L
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PACRITINIB HYDROCHLORIDE
Common Name English
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)
Systematic Name English
PACRITINIB MONOHYDROCHLORIDE
Common Name English
Code System Code Type Description
NCI_THESAURUS
C185888
Created by admin on Thu Jul 06 20:44:45 UTC 2023 , Edited by admin on Thu Jul 06 20:44:45 UTC 2023
PRIMARY
CAS
1228923-43-0
Created by admin on Thu Jul 06 20:44:45 UTC 2023 , Edited by admin on Thu Jul 06 20:44:45 UTC 2023
NON-SPECIFIC STOICHIOMETRY
FDA UNII
XV36F0JG6L
Created by admin on Thu Jul 06 20:44:45 UTC 2023 , Edited by admin on Thu Jul 06 20:44:45 UTC 2023
PRIMARY
PUBCHEM
67443473
Created by admin on Thu Jul 06 20:44:45 UTC 2023 , Edited by admin on Thu Jul 06 20:44:45 UTC 2023
PRIMARY
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ACTIVE MOIETY