DS-1001B
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MedKoo CAT#: 533299

CAS#: 1898207-64-1 (tBuA)

Description: DS-1001B is a novel selective mutant IDH1 inhibitor, ameliorating aberrant histone modifications and impairing tumor activity in chondrosarcoma.


Chemical Structure

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DS-1001B
CAS# 1898207-64-1 (tBuA)

Theoretical Analysis

MedKoo Cat#: 533299
Name: DS-1001B
CAS#: 1898207-64-1 (tBuA)
Chemical Formula: C29H29Cl3FN3O4
Exact Mass: 607.12
Molecular Weight: 608.916
Elemental Analysis: C, 57.20; H, 4.80; Cl, 17.47; F, 3.12; N, 6.90; O, 10.51

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2850 Ready to ship
1g USD 3950 2 weeks
2g USD 6450 2 weeks
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Related CAS #: 1898206-17-1 (free base)   1898207-64-1 ((tBuA)    

Synonym: DS-1001B; DS 1001B; DS1001B; DS-1001; DS 1001; DS1001.

IUPAC/Chemical Name: t-Butylamine (E)-3-(1-(5-(2-fluoropropan-2-yl)-3-(2,4,6-trichlorophenyl)isoxazole-4-carbonyl)-3-methyl-1H-indol-4-yl)acrylate

InChi Key: UPPAAWQBZQBNIE-USRGLUTNSA-N

InChi Code: InChI=1S/C25H18Cl3FN2O4.C4H11N/c1-12-11-31(17-6-4-5-13(19(12)17)7-8-18(32)33)24(34)21-22(30-35-23(21)25(2,3)29)20-15(27)9-14(26)10-16(20)28;1-4(2,3)5/h4-11H,1-3H3,(H,32,33);5H2,1-3H3/b8-7+;

SMILES Code: NC(C)(C)C.O=C(O)/C=C/C1=CC=CC2=C1C(C)=CN2C(C3=C(C(C)(F)C)ON=C3C4=C(Cl)C=C(Cl)C=C4Cl)=O

Appearance: 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

Shelf Life: >3 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

More Info:

Biological target: DS-1001b is a selective inhibitor of mutant IDH1 R132X.
In vitro activity: DS-1001b strongly inhibited mutant IDH1 but not wild-type IDH1. The role of mutant IDH1 in chondrosarcoma was investigated by assessing the effects of DS-1001b on chondrosarcoma cell lines with wild-type or mutant IDH. Sanger sequencing was performed to determine the presence of IDH mutations in the different cell lines. The heterozygous IDH mutation was detected in JJ012 (IDH1R132G), L835 (IDH1R132C), and SW1353 (IDH2R172S) cells (Supplementary Fig. 1A), whereas OUMS27 and NDCS-1 cells had no mutation in either allele (data not shown). Measurement of intracellular 2-HG by LC-MS/MS showed that 2-HG levels were significantly higher in IDH-mutated cell lines than in IDH wild-type cell lines, in which 2-HG was barely detectable (Fig. 1b). The levels of 2-HG did not differ significantly between mutant IDH1 and IDH2 cell lines. Exposure to 1 μM DS-1001b for 72 h markedly decreased intracellular 2-HG levels in JJ012 and L835 cells, whereas DS-1001b had no effect in SW1353, OUMS27, and NDCS-1 cells. Intracellular D-2-HG levels measured by LC-TOFMS were 100-fold higher than L-2-HG levels and completely blocked with 1 μM DS-1001b for 72 h in both IDH1-mutated cell lines (Fig. 1c). Reference: Oncogene. 2019 Oct;38(42):6835-6849. https://doi.org/10.1038/s41388-019-0929-9
In vivo activity: DS-1001b strongly inhibited mutant IDH1 but not wild-type IDH1. The role of mutant IDH1 in chondrosarcoma was investigated by assessing the effects of DS-1001b on chondrosarcoma cell lines with wild-type or mutant IDH. Sanger sequencing was performed to determine the presence of IDH mutations in the different cell lines. The heterozygous IDH mutation was detected in JJ012 (IDH1R132G), L835 (IDH1R132C), and SW1353 (IDH2R172S) cells (Supplementary Fig. 1A), whereas OUMS27 and NDCS-1 cells had no mutation in either allele (data not shown). Measurement of intracellular 2-HG by LC-MS/MS showed that 2-HG levels were significantly higher in IDH-mutated cell lines than in IDH wild-type cell lines, in which 2-HG was barely detectable (Fig. 1b). The levels of 2-HG did not differ significantly between mutant IDH1 and IDH2 cell lines. Exposure to 1 μM DS-1001b for 72 h markedly decreased intracellular 2-HG levels in JJ012 and L835 cells, whereas DS-1001b had no effect in SW1353, OUMS27, and NDCS-1 cells. Intracellular D-2-HG levels measured by LC-TOFMS were 100-fold higher than L-2-HG levels and completely blocked with 1 μM DS-1001b for 72 h in both IDH1-mutated cell lines (Fig. 1c). Reference: Oncogene. 2019 Oct;38(42):6835-6849. https://doi.org/10.1038/s41388-019-0929-9

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 14.0 22.99

Preparing Stock Solutions

The following data is based on the product molecular weight 608.92 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:
In vitro protocol: 1. Nakagawa M, Nakatani F, Matsunaga H, Seki T, Endo M, Ogawara Y, Machida Y, Katsumoto T, Yamagata K, Hattori A, Fujita S, Aikawa Y, Ishikawa T, Soga T, Kawai A, Chuman H, Yokoyama N, Fukushima S, Yahiro K, Kimura A, Shimada E, Hirose T, Fujiwara T, Setsu N, Matsumoto Y, Iwamoto Y, Nakashima Y, Kitabayashi I. Selective inhibition of mutant IDH1 by DS-1001b ameliorates aberrant histone modifications and impairs tumor activity in chondrosarcoma. Oncogene. 2019 Oct;38(42):6835-6849. doi: 10.1038/s41388-019-0929-9. Epub 2019 Aug 12. PMID: 31406254.
In vivo protocol: 1. Nakagawa M, Nakatani F, Matsunaga H, Seki T, Endo M, Ogawara Y, Machida Y, Katsumoto T, Yamagata K, Hattori A, Fujita S, Aikawa Y, Ishikawa T, Soga T, Kawai A, Chuman H, Yokoyama N, Fukushima S, Yahiro K, Kimura A, Shimada E, Hirose T, Fujiwara T, Setsu N, Matsumoto Y, Iwamoto Y, Nakashima Y, Kitabayashi I. Selective inhibition of mutant IDH1 by DS-1001b ameliorates aberrant histone modifications and impairs tumor activity in chondrosarcoma. Oncogene. 2019 Oct;38(42):6835-6849. doi: 10.1038/s41388-019-0929-9. Epub 2019 Aug 12. PMID: 31406254. 2. Machida Y, Nakagawa M, Matsunaga H, Yamaguchi M, Ogawara Y, Shima Y, Yamagata K, Katsumoto T, Hattori A, Itoh M, Seki T, Nishiya Y, Nakamura K, Suzuki K, Imaoka T, Baba D, Suzuki M, Sampetrean O, Saya H, Ichimura K, Kitabayashi I. A Potent Blood-Brain Barrier-Permeable Mutant IDH1 Inhibitor Suppresses the Growth of Glioblastoma with IDH1 Mutation in a Patient-Derived Orthotopic Xenograft Model. Mol Cancer Ther. 2020 Feb;19(2):375-383. doi: 10.1158/1535-7163.MCT-18-1349. Epub 2019 Nov 14. PMID: 31727689.

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