R1530
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MedKoo CAT#: 202391

CAS#: 882531-87-5

Description: R1530 is a pyrazolobenzodiazepine small molecule 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 agents exhibits anti-proliferative activity by initiating mitotic arrest and inducing apoptosis.


Chemical Structure

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R1530
CAS# 882531-87-5

Theoretical Analysis

MedKoo Cat#: 202391
Name: R1530
CAS#: 882531-87-5
Chemical Formula: C18H14ClFN4O
Exact Mass: 356.08402
Molecular Weight: 356.78
Elemental Analysis: C, 60.60; H, 3.96; Cl, 9.94; F, 5.32; N, 15.70; O, 4.48

Price and Availability

Size Price Availability Quantity
10.0mg USD 190.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 850.0 Ready to ship
200.0mg USD 1250.0 Ready to ship
500.0mg USD 2150.0 Ready to ship
1.0g USD 2950.0 2 weeks
2.0g USD 3950.0 2 weeks
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Synonym: R1530; R-1530; R 1530.

IUPAC/Chemical Name: 5-(2-chlorophenyl)-7-fluoro-8-methoxy-3-methyl-2,10-dihydrobenzo[e]pyrazolo[4,3-b][1,4]diazepine

InChi Key: UOVCGJXDGOGOCZ-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: CC1=C2N=C(C3=CC=CC=C3Cl)C4=CC(F)=C(OC)C=C4NC2=NN1

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: R1530 is a multikinase inhibitor which binds to 31 kinases with Kds of <500 nM. R1530 inhibits VGFR2 and FGFR1 with IC50s of 10 nM and 28 nM, respectively.
In vitro activity: 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, colon, lung, prostate, melanoma, and oral epidermoid (Supplementary Table 2 in the Supporting Information). R1530 exhibited potent in vitro antiproliferative activity in all of the tumor cell lines tested (IC50 = 0.2–3.4 μM). Because of its ability to inhibit the kinase activities of vascular endothelial growth factor receptor 2 (VGFr2), FGFr1, and PDGFr-β, R1530 was further characterized for its effects on VEGF and bFGF-induced proliferation of human umbilical vein endothelial cells (HUVEC) and PDGF driven fibroblast proliferation. R1530 showed strong inhibition of VEGF and bFGF induced HUVEC proliferation (IC50 = 49 and 118 nM); however, activity in the PDGF driven assay was less potent (IC50 = 688 nM). Reference: ACS Med Chem Lett. 2013 Feb 14; 4(2): 259–263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027509/
In vivo activity: Figure 1 illustrates the effect of once-daily R1530 on tumor growth in the H460 human NSCLC xenograft model. The lowest dose at which significant antitumor activity was observed was 3.125 mg/kg qd (72% TGI, P < 0.001). At 6.25 and 12.5 mg/kg, TGIs of 83% (P < 0.001) and 92% (P < 0.001), respectively, were seen. At the higher doses of 25 and 50 mg/kg qd, 96% TGI (P < 0.001, with 2/9 partial responses [PRs]) and >100% TGI (P < 0.001, 9/10 PRs and 1/10 complete regressions [CRs]) were observed, respectively (Fig. 1a). Tumors exposed to R1530 were smaller and paler in appearance than tumors from mice treated with vehicle (see supplementary information). This observation is consistent with the anti-angiogenic activity attributed to R1530. Reference: Cancer Chemother Pharmacol. 2011 Dec;68(6):1585-94. https://pubmed.ncbi.nlm.nih.gov/21553286/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 30.0 84.1
Ethanol 20.0 56.1

Preparing Stock Solutions

The following data is based on the product molecular weight 356.78 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Liu JJ, Higgins B, Ju G, Kolinsky K, Luk KC, Packman K, Pizzolato G, Ren Y, Thakkar K, Tovar C, Zhang Z, Wovkulich PM. Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors. ACS Med Chem Lett. 2013 Jan 15;4(2):259-63. doi: 10.1021/ml300351e. PMID: 24900658; PMCID: PMC4027509. 2. Kolinsky K, Tovar C, Zhang YE, Railkar A, Yang H, Carvajal D, Nevins T, Geng W, Linn M, Packman K, Liu JJ, Zhang Z, Wovkulich P, Ju G, Higgins B. Preclinical evaluation of the novel multi-targeted agent R1530. Cancer Chemother Pharmacol. 2011 Dec;68(6):1585-94. doi: 10.1007/s00280-011-1608-x. Epub 2011 May 8. PMID: 21553286.
In vitro protocol: 1. Liu JJ, Higgins B, Ju G, Kolinsky K, Luk KC, Packman K, Pizzolato G, Ren Y, Thakkar K, Tovar C, Zhang Z, Wovkulich PM. Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors. ACS Med Chem Lett. 2013 Jan 15;4(2):259-63. doi: 10.1021/ml300351e. PMID: 24900658; PMCID: PMC4027509. 2. Kolinsky K, Tovar C, Zhang YE, Railkar A, Yang H, Carvajal D, Nevins T, Geng W, Linn M, Packman K, Liu JJ, Zhang Z, Wovkulich P, Ju G, Higgins B. Preclinical evaluation of the novel multi-targeted agent R1530. Cancer Chemother Pharmacol. 2011 Dec;68(6):1585-94. doi: 10.1007/s00280-011-1608-x. Epub 2011 May 8. PMID: 21553286.
In vivo protocol: 1. Liu JJ, Higgins B, Ju G, Kolinsky K, Luk KC, Packman K, Pizzolato G, Ren Y, Thakkar K, Tovar C, Zhang Z, Wovkulich PM. Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors. ACS Med Chem Lett. 2013 Jan 15;4(2):259-63. doi: 10.1021/ml300351e. PMID: 24900658; PMCID: PMC4027509. 2. Kolinsky K, Tovar C, Zhang YE, Railkar A, Yang H, Carvajal D, Nevins T, Geng W, Linn M, Packman K, Liu JJ, Zhang Z, Wovkulich P, Ju G, Higgins B. Preclinical evaluation of the novel multi-targeted agent R1530. Cancer Chemother Pharmacol. 2011 Dec;68(6):1585-94. doi: 10.1007/s00280-011-1608-x. Epub 2011 May 8. PMID: 21553286.

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R1530

10.0mg / USD 190.0


Additional Information

 
Preclinical study of R1350 (data published in 2011): Reclinical study showed that R1530 strongly inhibited human tumor cell proliferation. Growth factor-driven proliferation of endothelial and fibroblast cells was also inhibited. 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 (3.125-50 mg/kg qd, 100 mg/kg qw, 100 mg/kg biw). 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 (50 mg/kg). 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. Exposure was dose dependent up to 100 mg/kg with oral administration. R1530 has demonstrated activity against a range of tumor models in vitro and in vivo and is an effective inhibitor of angiogenesis. These findings support the approach of targeting multiple pathways in the search for potential agents with improved anticancer properties. (source: Cancer Chemother Pharmacol. 2011 Dec;68(6):1585-94.).