Details of the Drug

General Information of Drug (ID: DM1T6ZN)

Drug Name
Pacritinib
Synonyms JAK inhibitor (alone or in combination)s
Indication
Disease Entry ICD 11 Status REF
Myelofibrosis 2A20.2 Phase 3 [1], [2], [3], [4]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 472.6
Topological Polar Surface Area (xlogp) 3.8
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 7
Chemical Identifiers
Formula
C28H32N4O3
IUPAC Name
(16E)-11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,27-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(24),2(27),3,5,8(26),9,11,16,21(25),22-decaene
Canonical SMILES
C1CCN(C1)CCOC2=C3COC/C=C/COCC4=CC(=CC=C4)C5=NC(=NC=C5)NC(=C3)C=C2
InChI
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+
InChIKey
HWXVIOGONBBTBY-ONEGZZNKSA-N
Cross-matching ID
PubChem CID
46216796
CAS Number
937272-79-2
DrugBank ID
DB11697
TTD ID
D0PN8H

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Fms-like tyrosine kinase 3 (FLT-3) TTGJCWZ FLT3_HUMAN Modulator [5]
Janus kinase 2 (JAK-2) TTRMX3V JAK2_HUMAN Modulator [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Myelofibrosis
ICD Disease Classification 2A20.2
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Fms-like tyrosine kinase 3 (FLT-3) DTT FLT3 2.11E-01 -0.05 -0.16
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7793).
2 Clinical pipeline report, company report or official report of CTI BioPharma.
3 ClinicalTrials.gov (NCT02055781) Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia. U.S. National Institutes of Health.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1807).
6 National Cancer Institute Drug Dictionary (drug id 609888).
7 Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.
8 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
10 Genetic determinants of response and survival in momelotinib-treated patients with myelofibrosis.Leukemia.2015 Mar;29(3):741-4.
11 Emerging drugs for the therapy of primary and post essential thrombocythemia, post polycythemia vera myelofibrosis. Expert Opin Emerg Drugs. 2009 Sep;14(3):471-9.
12 Company report (Portola Pharmaceuticals)
13 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
14 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2048).
15 Clinical pipeline report, company report or official report of Concert Pharmaceuticals.
16 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
17 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
18 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
19 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
20 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
21 Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with ... Blood. 2008 Jun 15;111(12):5663-71.
22 Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
23 Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93.