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Details

Stereochemistry ACHIRAL
Molecular Formula C26H32N6O2
Molecular Weight 460.5723
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of JNJ-28312141 FREE BASE

SMILES

CN(C)CC(=O)N1CCC(CC1)c2ccc(c(c2)C3=CCCCC3)NC(=O)c4ncc(C#N)[nH]4

InChI

InChIKey=GUBJNPWVIUFSTR-UHFFFAOYSA-N
InChI=1S/C26H32N6O2/c1-31(2)17-24(33)32-12-10-18(11-13-32)20-8-9-23(22(14-20)19-6-4-3-5-7-19)30-26(34)25-28-16-21(15-27)29-25/h6,8-9,14,16,18H,3-5,7,10-13,17H2,1-2H3,(H,28,29)(H,30,34)

HIDE SMILES / InChI

Molecular Formula C26H32N6O2
Molecular Weight 460.5723
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

JNJ-28312141 is an orally active colony-stimulating factor-1 receptor and FMS-related receptor tyrosine kinase-3 inhibitor. In preclinical models, JNJ-28312141 caused regression of ITD-FLT3–dependent MV-4-11 AML xenografts. The drug also suppressed the growth of H460 non-small cell lung adenocarcinoma xenografts and inhibited osteoclastogenesis and osteolysis in a rat model of metastatic bone disease.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.69 nM [IC50]
30.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia.
2009 Nov
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Optimization of a potent class of arylamide colony-stimulating factor-1 receptor inhibitors leading to anti-inflammatory clinical candidate 4-cyano-N-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1H-imidazole-2-carboxamide (JNJ-28312141).
2011 Nov 24
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Patents

Sample Use Guides

NCI-H460 human non–small cell lung adenocarcinoma cells were suspended at 1 × 107 cells/mL in sterile PBS, and 100 μL were injected s.c. into the left inguinal region of female (9–10 wk old) CD-1 nu/nu mice. Three days later, mice were randomized into four groups (15 per group) and p.o. gavage dosing was initiated with vehicle (HPβCD) or with JNJ-28312141 at doses of 25, 50, and 100 mg/kg. Dosing was twice daily during the week and once daily on weekends for 25 consecutive days. JNJ-28312141 dose-dependently inhibited tumor growth.
Route of Administration: Oral
Cell proliferation dependent on FLT3, KIT, and TRKA was assessed using MV-4-11 AML cells (ATCC CRL-9591), Mo7e erythroleukemia cells (DSMZ ACC-104), and TF-1 myeloid leukemia cells (ATCC CRL-2003), respectively. Cells were dispensed into microtiter plates (10,000 per well) together with graded concentrations of JNJ-28312141. Mo7e and TF-1 cultures were adjusted to contain 25 ng/mL stem cell factor or 1.4 ng/mL nerve growth factor, respectively. MV-4-11 cells were growth factor independent, due to an internal tandem duplication (ITD) of the FLT3 juxtamembrane domain, rendering FLT3 constitutively active (21). After a 72-h culture period, relative cell numbers were determined using CellTiterGlo reagent (Promega). MV-4-11 growth was calculated based on the difference between luminescence on day 3 versus day 0. M-07e and TF-1 growth was calculated based on the difference in luminescence of cells cultured in the presence versus the absence of growth factor. JNJ-28312141 inhibited the ITD-FLT3–dependent proliferation of MV-4-11 cells (IC50, 0.021 μmol/L), KIT-dependent proliferation of Mo7e cells (IC50, 0.041 μmol/L), and TRKA-dependent proliferation of TF-1 cells (IC50, 0.15 μmol/L).
Substance Class Chemical
Created
by admin
on Sat Jun 26 12:26:39 UTC 2021
Edited
by admin
on Sat Jun 26 12:26:39 UTC 2021
Record UNII
YKQ241VJ92
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
JNJ-28312141 FREE BASE
Common Name English
1H-IMIDAZOLE-2-CARBOXAMIDE, 5-CYANO-N-(2-(1-CYCLOHEXEN-1-YL)-4-(1-(2-(DIMETHYLAMINO)ACETYL)-4-PIPERIDINYL)PHENYL)-
Systematic Name English
Code System Code Type Description
FDA UNII
YKQ241VJ92
Created by admin on Sat Jun 26 12:26:40 UTC 2021 , Edited by admin on Sat Jun 26 12:26:40 UTC 2021
PRIMARY
EPA CompTox
885692-52-4
Created by admin on Sat Jun 26 12:26:40 UTC 2021 , Edited by admin on Sat Jun 26 12:26:40 UTC 2021
PRIMARY
PUBCHEM
11676971
Created by admin on Sat Jun 26 12:26:40 UTC 2021 , Edited by admin on Sat Jun 26 12:26:40 UTC 2021
PRIMARY
CAS
885692-52-4
Created by admin on Sat Jun 26 12:26:40 UTC 2021 , Edited by admin on Sat Jun 26 12:26:40 UTC 2021
PRIMARY
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