Details
Stereochemistry | ACHIRAL |
Molecular Formula | C29H35N7O4.2ClH |
Molecular Weight | 618.555 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.COCCN1CCN(CC2=CC=C(C=C2)C3=NNC4=C3C(=O)C5=C4C=CC=C5NC(=O)NN6CCOCC6)CC1
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
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 |
Molecular Formula | ClH |
Molecular Weight | 36.461 |
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/25024258
https://www.ncbi.nlm.nih.gov/pubmed/23807770
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3116 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23807770 |
1.0 nM [IC50] | ||
Target ID: CHEMBL308 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23807770 |
2.0 nM [IC50] | ||
Target ID: CHEMBL301 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23807770 |
3.0 nM [IC50] | ||
Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23807770 |
4.0 nM [IC50] | ||
Target ID: CHEMBL4036 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23807770 |
5.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1297 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25024258/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25024258/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25024258/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25024258/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25024258/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25024258/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25024258/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25024258/ |
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25024258
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23807770
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
Edited
Fri Dec 15 19:05:28 GMT 2023
by
admin
on
Fri Dec 15 19:05:28 GMT 2023
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Record UNII |
478ZV54680
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Record Status |
Validated (UNII)
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Record Version |
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CHEMBL3545083
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DTXSID40229071
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784210-87-3
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11285001
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478ZV54680
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300000042505
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PARENT -> SALT/SOLVATE |