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Details

Stereochemistry ACHIRAL
Molecular Formula C28H32N4O3
Molecular Weight 472.5797
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PACRITINIB

SMILES

C1CCN(C1)CCOc2ccc3cc2COC/C(/[H])=C(\[H])/COCc4cccc(c4)-c5ccnc(N3)n5

InChI

InChIKey=HWXVIOGONBBTBY-ONEGZZNKSA-N
InChI=1S/C28H32N4O3/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)/b4-3+

HIDE SMILES / InChI

Molecular Formula C28H32N4O3
Molecular Weight 472.5797
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 Sat Jun 26 11:30:30 UTC 2021
Edited
by admin
on Sat Jun 26 11:30:30 UTC 2021
Record UNII
G22N65IL3O
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PACRITINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
SB-1518
Code 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)-, (16E)-
Systematic Name English
SB1518
Code English
PACRITINIB [INN]
Common Name English
PACRITINIB [USAN]
Common Name English
PACRITINIB [WHO-DD]
Common Name English
ONX-0803
Code English
Classification Tree Code System Code
EU-Orphan Drug EU/3/10/767
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
NCI_THESAURUS C125450
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
FDA ORPHAN DRUG 245607
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
Code System Code Type Description
DRUG BANK
DB11697
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
PRIMARY
PUBCHEM
46216796
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
PRIMARY
EVMPD
SUB114513
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
PRIMARY
FDA UNII
G22N65IL3O
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
PRIMARY
CAS
937272-79-2
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
PRIMARY
NCI_THESAURUS
C78837
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
PRIMARY
INN
9385
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
PRIMARY
EU-Orphan Drug
EU/3/10/767(POSITIVE)
Created by admin on Sat Jun 26 11:30:31 UTC 2021 , Edited by admin on Sat Jun 26 11:30:31 UTC 2021
PRIMARY On 25 August 2010, orphan designation (EU/3/10/767) was granted by the European Commission to Voisin Consulting S.A.R.L., France, for 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 for the treatment of post-essential thrombocythaemia myelofibrosis. The sponsorship was transferred to Baxter Innovations GmbH, Austria, in March 2015. In May 2015, Baxter Innovations GmbH changed name to Baxalta Innovations GmbH. The sponsorship was transferred to CTI Life Sciences Ltd, United Kingdom, in November 2016.
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