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Details

Stereochemistry ACHIRAL
Molecular Formula C29H35N7O4
Molecular Weight 545.6327
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RGB-286638 FREE BASE

SMILES

COCCN1CCN(CC2=CC=C(C=C2)C3=NNC4=C3C(=O)C5=C4C=CC=C5NC(=O)NN6CCOCC6)CC1

InChI

InChIKey=XLSYZSRXVVCHLS-UHFFFAOYSA-N
InChI=1S/C29H35N7O4/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)

HIDE SMILES / InChI

Molecular Formula C29H35N7O4
Molecular Weight 545.6327
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
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 Fri Dec 15 18:46:26 GMT 2023
Edited
by admin
on Fri Dec 15 18:46:26 GMT 2023
Record UNII
1GAJ98SC2X
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RGB-286638 FREE BASE
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-
Systematic Name English
Code System Code Type Description
EPA CompTox
DTXSID00229072
Created by admin on Fri Dec 15 18:46:26 GMT 2023 , Edited by admin on Fri Dec 15 18:46:26 GMT 2023
PRIMARY
CAS
784210-88-4
Created by admin on Fri Dec 15 18:46:26 GMT 2023 , Edited by admin on Fri Dec 15 18:46:26 GMT 2023
PRIMARY
FDA UNII
1GAJ98SC2X
Created by admin on Fri Dec 15 18:46:26 GMT 2023 , Edited by admin on Fri Dec 15 18:46:26 GMT 2023
PRIMARY
PUBCHEM
11285002
Created by admin on Fri Dec 15 18:46:26 GMT 2023 , Edited by admin on Fri Dec 15 18:46:26 GMT 2023
PRIMARY
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