Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C23H22N6O2 |
| Molecular Weight | 414.4598 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C(NCC#N)C1=CC=C(C=C1)C2=NC(NC3=CC=C(C=C3)N4CCOCC4)=NC=C2
InChI
InChIKey=ZVHNDZWQTBEVRY-UHFFFAOYSA-N
InChI=1S/C23H22N6O2/c24-10-12-25-22(30)18-3-1-17(2-4-18)21-9-11-26-23(28-21)27-19-5-7-20(8-6-19)29-13-15-31-16-14-29/h1-9,11H,12-16H2,(H,25,30)(H,26,27,28)
| Molecular Formula | C23H22N6O2 |
| Molecular Weight | 414.4598 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/19295546 | https://www.ncbi.nlm.nih.gov/pubmed/23459451
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/19295546 | https://www.ncbi.nlm.nih.gov/pubmed/23459451
Momelotinib (CYT387) is an ATP-competitive small molecule that potently inhibits JAK1/JAK2 kinases. Momelotinib is developing by Gilead Sciences for the oral treatment of pancreatic and non-small cell lung cancers, and myeloproliferative disorders (including myelofibrosis, essential thrombocythaemia and polycythaemia vera).
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2835 |
11.0 nM [IC50] | ||
Target ID: CHEMBL2971 |
18.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator​
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes [IC50 5.8048 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs). | 2009 Oct 15 |
|
| CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. | 2010 Jun 24 |
|
| Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. | 2014 Apr |
|
| Momelotinib treatment-emergent neuropathy: prevalence, risk factors and outcome in 100 patients with myelofibrosis. | 2015 Apr |
|
| Momelotinib in myelofibrosis: JAK1/2 inhibitor with a role in treating and understanding the anemia. | 2017 Feb |
|
| A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis. | 2017 Jan |
Patents
Sample Use Guides
150-300 mg/day. Maximum tolerated dose of momelotinib was found to be 300 mg/day in the phase I portion of a phase I/II study (NCT00935987) in patients with myelofibrosis. At the higher dose level of 400 mg/day, two of six patients experienced dose-limiting toxicities.
Route of Administration:
Oral
| Substance Class |
Chemical
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311610
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| Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
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TARGET -> INHIBITOR |
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SALT/SOLVATE -> PARENT |
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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METABOLIC ENZYME -> SUBSTRATE |
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TARGET -> INHIBITOR |
IC50
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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TARGET -> INHIBITOR |
IC50
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EXCRETED UNCHANGED |
AMOUNT EXCRETED
FECAL
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EXCRETED UNCHANGED |
MINOR
URINE
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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METABOLIC ENZYME -> SUBSTRATE |
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SALT/SOLVATE -> PARENT |
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TARGET->WEAK INHIBITOR |
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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METABOLITE -> PARENT |
URINE
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METABOLITE -> PARENT |
PLASMA
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METABOLITE -> PARENT |
PLASMA
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METABOLITE ACTIVE -> PRODRUG |
MAJOR
URINE
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METABOLITE -> PARENT |
FECAL
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METABOLITE -> PARENT |
URINE
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METABOLITE -> PARENT |
M19 coelute with M33 (m/z = 431.1469, oxidative metabolite of MMB) in human feces.
FECAL
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METABOLITE -> PARENT |
URINE
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METABOLITE ACTIVE -> PARENT |
Metabolite M21 was 2- to 3-fold less active than MMB for inhibition of JAK1/2 and ACVR1 in vitro. However, on the basis of the PAI assessment, M21 is anticipated to contribute significantly to the pharmacological activity of MMB, not only as a JAK1/2 inhibitor but also as an ACVR1 inhibitor
MAJOR
PLASMA
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
MAJOR
FECAL
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METABOLITE ACTIVE -> PARENT |
MAJOR
FECAL
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METABOLITE -> PARENT |
FECAL
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METABOLITE -> PARENT |
URINE
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
PLASMA
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METABOLITE -> PARENT |
PLASMA
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METABOLITE -> PARENT |
URINE
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METABOLITE -> PARENT |
FECAL
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![Structure of 4-[2-[(4-Aminophenyl)amino]-4-pyrimidinyl]-N-(cyanomethyl)benzamide](/img/4dcdccfe-50ce-4151-92a0-636661d35b06.svg "Structure of 4-[2-[(4-Aminophenyl)amino]-4-pyrimidinyl]-N-(cyanomethyl)benzamide")
| Related Record | Type | Details | ||
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ACTIVE MOIETY |
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
|---|---|---|---|---|---|---|
| Tmax | PHARMACOKINETIC |
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| Biological Half-life | PHARMACOKINETIC |
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