Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H14ClFN4O |
Molecular Weight | 356.781 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=C(F)C=C2C(NC3=NNC(C)=C3N=C2C4=C(Cl)C=CC=C4)=C1
InChI
InChIKey=UOVCGJXDGOGOCZ-UHFFFAOYSA-N
InChI=1S/C18H14ClFN4O/c1-9-16-18(24-23-9)21-14-8-15(25-2)13(20)7-11(14)17(22-16)10-5-3-4-6-12(10)19/h3-8H,1-2H3,(H2,21,23,24)
Molecular Formula | C18H14ClFN4O |
Molecular Weight | 356.781 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/24900658Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21553286
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900658
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21553286
R1530 is the multikinase inhibitor with potential antiangiogenesis and antineoplastic activities. R1530 is also a mitosis-angiogenesis inhibitor (MAI) that inhibits multiple receptor tyrosine kinases involved in angiogenesis, such as vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, platelet-derived growth factor receptor (PDGFR) beta, FMS-like tyrosine kinase (Flt)-3, and fibroblast growth factor receptor (FGFR) -1, -2. In addition, this agent exhibits anti-proliferative activity by initiating mitotic arrest and inducing apoptosis. In the presence of R1530, polyploid cancer cells underwent apoptosis or became senescent which translated into potent in vitro and in vivo efficacy. Normal proliferating cells were resistant to R1530-induced polyploidy thus supporting the rationale for cancer therapy by induced polyploidy. Mitotic checkpoint kinase BubR1 was found downregulated during R1530-induced exit from mitosis, a likely consequence of PLK4 inhibition. R1530 strongly inhibited human tumor cell proliferation and growth factor-driven proliferation of endothelial and fibroblast cells. Significant tumor growth inhibition was demonstrated in a lung cancer xenograft model with a range of once daily, weekly and twice-weekly doses of R1530. Daily doses were most effective in the lung cancer model and also had significant growth inhibitory effects in models of colorectal, prostate, and breast tumors. Tumor regression occurred in all models treated with the maximum tolerated daily dose. The doses of 25 and 50 mg/kg QD resulted in biologically significant increased survival in all tested models. After oral administration in nude mice, R1530 showed good tissue penetration. R1530 had been in phase I clinical trials by Hoffmann-La Roche, Inc. for the treatment of advanced solid tumors. However, the clinical development of R1530 was discontinued.
Originator
Sources: https://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=2006079511A1&KC=A1&FT=D
Curator's Comment: # Hoffmann-La Roche Inc.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900658 |
28.0 nM [IC50] | ||
Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900658 |
10.0 nM [IC50] | ||
Target ID: CHEMBL301 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900658 |
1330.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00493155
In Phase 1 clinical trials R1530 has been administered daily for 14 days at the starting dose. This dose has been escalated in subsequent cohorts of patients, after a satisfactory assessment of safety and tolerability of the previous dose, until the maximum tolerated dose is reached.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900658
The in vitro antiproliferative effects of R1530 were further evaluated by the tetrazolium dye assay (MTT) in human tumor cell lines originating from various human tumor tissues including breast (MDA-MB-435), colon (HCT116, HT-29, HCT15), lung (H460a), prostate (DU-145, nrv 1, PC-3), melanoma (Lox), and oral epidermoid (KB-3-1). R1530 exhibited potent in vitro antiproliferative activity in all of the tumor cell lines tested (IC50 = 0.2−3.4 μM).
Substance Class |
Chemical
Created
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admin
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Edited
Fri Dec 15 15:34:29 GMT 2023
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Fri Dec 15 15:34:29 GMT 2023
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Record UNII |
XQJ55R5PPQ
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Record Status |
Validated (UNII)
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Record Version |
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CHEMBL1980391
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135398512
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XQJ55R5PPQ
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882531-87-5
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admin on Fri Dec 15 15:34:29 GMT 2023 , Edited by admin on Fri Dec 15 15:34:29 GMT 2023
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