Details
Stereochemistry | ACHIRAL |
Molecular Formula | C28H32N4O3 |
Molecular Weight | 472.5787 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C(CN1CCCC1)OC2=CC=C3C=C2COC\C=C\COCC4=CC(=CC=C4)C5=CC=NC(N5)=N3
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+
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 |
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
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21691275 |
23.0 nM [IC50] | ||
Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21691275 |
22.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator​
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no [IC50 >5 uM] | ||||
no [IC50 >5 uM] | ||||
no [IC50 >5 uM] | ||||
no [IC50 >5 uM] | ||||
no [IC50 >5 uM] | ||||
yes [IC50 4.6109 uM] | ||||
yes [Inhibition 10 uM] | ||||
yes [Inhibition 10 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25600203/ |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25600203/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
no | ||||
no |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02055781
Pacritinib 400 mg taken orally, once daily
Pacritinib 200 mg taken orally, twice daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22829080
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
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Record UNII |
G22N65IL3O
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Validated (UNII)
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EU-Orphan Drug |
EU/3/10/767
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245607
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C125450
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C129825
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EU/3/10/767(POSITIVE)
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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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Pacritinib
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
IC50
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SALT/SOLVATE -> PARENT |
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TRANSPORTER -> INHIBITOR |
IC50
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TRANSPORTER -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
IC50
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TRANSPORTER -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
IC50
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
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OFF-TARGET->INHIBITOR |
IC50
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TARGET -> INHIBITOR |
IC50
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Related Record | Type | Details | ||
---|---|---|---|---|
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METABOLITE LESS ACTIVE -> PARENT |
Predominant Metabolite in human studies
MAJOR
FECAL; PLASMA; URINE
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METABOLITE -> PARENT |
MINOR
PLASMA; URINE
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METABOLITE INACTIVE -> PARENT |
MINOR
FECAL
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METABOLITE -> PARENT |
FECAL; PLASMA; URINE
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METABOLITE INACTIVE -> PARENT |
MINOR
FECAL
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METABOLITE INACTIVE -> PARENT |
MINOR
FECAL
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METABOLITE -> PARENT |
PLASMA; URINE
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METABOLITE LESS ACTIVE -> PARENT |
Major metabolite in animal species lesser metabolite in human studies. Has 50% of the activity of the parent
MAJOR
PLASMA
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METABOLITE INACTIVE -> PARENT |
MINOR
FECAL
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METABOLITE -> PARENT |
FECAL; PLASMA; URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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