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Details

Stereochemistry ACHIRAL
Molecular Formula C29H35N7O4.2ClH
Molecular Weight 618.5556
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RGB-286638

SMILES

COCCN1CCN(CC1)Cc2ccc(cc2)-c3c4c(-c5cccc(c5C4=O)N=C(NN6CCOCC6)O)[nH]n3.Cl.Cl

InChI

InChIKey=WJVMGQMXUBAAPL-UHFFFAOYSA-N
InChI=1S/C29H35N7O4.2ClH/c1-39-16-13-34-9-11-35(12-10-34)19-20-5-7-21(8-6-20)26-25-27(32-31-26)22-3-2-4-23(24(22)28(25)37)30-29(38)33-36-14-17-40-18-15-36;;/h2-8H,9-19H2,1H3,(H,31,32)(H2,30,33,38);2*1H

HIDE SMILES / InChI

Molecular Formula C29H35N7O4
Molecular Weight 545.6338
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25024258 https://www.ncbi.nlm.nih.gov/pubmed/23807770

RGB-286638 is a multi-targeted protein kinase inhibitor currently in Phase 1 clinical testing. In vitro cell-free kinase assays indicated that RGB-286638 inhibits CDK1, 2, 3, 4, 5, and 9 and is less active against CDK6 and 7. The RGB-286638 compound has been shown to inhibit the processes controlling cell division in cancer cells by targeting multiple cyclin-dependent kinase proteins involved in regulating the cell cycle. RGB-286638 has also been shown to induce apoptosis (programmed cell death) and to inhibit other important protein kinases involved in the proliferation of cancer cells. RGB-286638 treatment results in tumor regression and increased survival in a number of pre-clinical models of solid and hematological tumors.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.0 nM [IC50]
2.0 nM [IC50]
3.0 nM [IC50]
4.0 nM [IC50]
5.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1297 μg × h/mL
80 mg single, intravenous
dose: 80 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
RGB-286638 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2026 μg × h/mL
120 mg single, intravenous
dose: 120 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
RGB-286638 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2307 μg × h/mL
160 mg single, intravenous
dose: 160 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
RGB-286638 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
275 μg × h/mL
20 mg single, intravenous
dose: 20 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
RGB-286638 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9.1 h
80 mg single, intravenous
dose: 80 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
RGB-286638 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9.3 h
120 mg single, intravenous
dose: 120 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
RGB-286638 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7.87 h
160 mg single, intravenous
dose: 160 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
RGB-286638 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8.35 h
20 mg single, intravenous
dose: 20 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
RGB-286638 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs.
2013 Dec
Phase I study of RGB-286638, a novel, multitargeted cyclin-dependent kinase inhibitor in patients with solid tumors.
2014 Sep 15
Patents

Sample Use Guides

The dose levels studied were 10, 20, 40, 80, 120, and 160 mg administered i.v. on days 1 to 5 within 1 hour, with cycles repeated once every 28 days. In this first in human phase I study in patients with solid tumors the recommended dose of RGB-286638 for phase II studies was identified at 120 mg/d i.v. at 1 to 5 days every 4 weeks, given through a central venous line preceded by antiemetics.
Route of Administration: Intravenous
Time-course immunoblot analysis revealed that 50nM RGB-286638 treatment decreased cyclins (A, B1, D1, and D3), CDK1, and CDK4 expression in MM.1S cells, and reduced cyclin A and D1 levels slightly in U266 cells within 8h.
Substance Class Chemical
Created
by admin
on Sat Jun 26 00:50:51 UTC 2021
Edited
by admin
on Sat Jun 26 00:50:51 UTC 2021
Record UNII
478ZV54680
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RGB-286638
Common Name English
UREA, N-(1,4-DIHYDRO-3-(4-((4-(2-METHOXYETHYL)-1-PIPERAZINYL)METHYL)PHENYL)-4-OXOINDENO(1,2-C)PYRAZOL-5-YL)-N'-4-MORPHOLINYL-, HYDROCHLORIDE (1:2)
Systematic Name English
UREA, N-(1,4-DIHYDRO-3-(4-((4-(2-METHOXYETHYL)-1-PIPERAZINYL)METHYL)PHENYL)-4-OXOINDENO(1,2-C)PYRAZOL-5-YL)-N'-4-MORPHOLINYL-, DIHYDROCHLORIDE
Common Name English
RGB 286638
Code English
Code System Code Type Description
ChEMBL
CHEMBL3545083
Created by admin on Sat Jun 26 00:50:51 UTC 2021 , Edited by admin on Sat Jun 26 00:50:51 UTC 2021
PRIMARY
EPA CompTox
784210-87-3
Created by admin on Sat Jun 26 00:50:51 UTC 2021 , Edited by admin on Sat Jun 26 00:50:51 UTC 2021
PRIMARY
CAS
784210-87-3
Created by admin on Sat Jun 26 00:50:51 UTC 2021 , Edited by admin on Sat Jun 26 00:50:51 UTC 2021
PRIMARY
PUBCHEM
11285001
Created by admin on Sat Jun 26 00:50:51 UTC 2021 , Edited by admin on Sat Jun 26 00:50:51 UTC 2021
PRIMARY
FDA UNII
478ZV54680
Created by admin on Sat Jun 26 00:50:51 UTC 2021 , Edited by admin on Sat Jun 26 00:50:51 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
TARGET -> INHIBITOR
PARENT -> SALT/SOLVATE