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Details

Stereochemistry ACHIRAL
Molecular Formula C26H32N6O2
Molecular Weight 460.5713
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)C2=CC=C(NC(=O)C3=NC(=CN3)C#N)C(=C2)C4=CCCCC4

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 460.5713
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
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 Dec 17 13:38:13 UTC 2022
Edited
by admin
on Sat Dec 17 13:38:13 UTC 2022
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 Dec 17 13:38:13 UTC 2022 , Edited by admin on Sat Dec 17 13:38:13 UTC 2022
PRIMARY
EPA CompTox
DTXSID70237129
Created by admin on Sat Dec 17 13:38:13 UTC 2022 , Edited by admin on Sat Dec 17 13:38:13 UTC 2022
PRIMARY
PUBCHEM
11676971
Created by admin on Sat Dec 17 13:38:13 UTC 2022 , Edited by admin on Sat Dec 17 13:38:13 UTC 2022
PRIMARY
CAS
885692-52-4
Created by admin on Sat Dec 17 13:38:13 UTC 2022 , Edited by admin on Sat Dec 17 13:38:13 UTC 2022
PRIMARY
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