BSJ-4-116
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MedKoo CAT#: 40163

CAS#: 2519823-34-6

Description: BSJ-4-116 is a highly potent and selective CDK12 degrader (PROTAC) with an IC50 of 6 nM. BSJ-4-116 selectively degraded CDK12 as assessed through quantitative proteomics. Selective degradation of CDK12 resulted in premature cleavage and poly(adenylation) of DDR genes. Moreover, BSJ-4-116 exhibited potent antiproliferative effects, alone and in combination with the poly(ADP-ribose) polymerase inhibitor olaparib, as well as when used as a single agent against cell lines resistant to covalent CDK12 inhibitors. Two point mutations in CDK12 were identified that confer resistance to BSJ-4-116, demonstrating a potential mechanism that tumor cells can use to evade bivalent degrader.


Chemical Structure

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BSJ-4-116
CAS# 2519823-34-6

Theoretical Analysis

MedKoo Cat#: 40163
Name: BSJ-4-116
CAS#: 2519823-34-6
Chemical Formula: C40H49ClN8O8S
Exact Mass: 836.3083
Molecular Weight: 837.39
Elemental Analysis: C, 57.37; H, 5.90; Cl, 4.23; N, 13.38; O, 15.28; S, 3.83

Price and Availability

Size Price Availability Quantity
50.0mg USD 850.0 2 Weeks
100.0mg USD 1450.0 2 Weeks
200.0mg USD 2250.0 2 Weeks
500.0mg USD 3650.0 2 Weeks
1.0g USD 5450.0 2 Weeks
2.0g USD 9450.0 2 Weeks
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Synonym: BSJ-4-116; BSJ4-116; BSJ 4-116; BSJ-4116; BSJ4116; BSJ 4116;

IUPAC/Chemical Name: Acetamide, N-[7-[(3R)-3-[[5-chloro-4-[[2-[(1-methylethyl)sulfonyl]phenyl]amino]-2-pyrimidinyl]amino]-1-piperidinyl]heptyl]-2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]-

InChi Key: YJOJMGTVKMABKQ-FIQOPJFZSA-N

InChi Code: InChI=1S/C40H49ClN8O8S/c1-25(2)58(55,56)32-16-7-6-14-29(32)45-36-28(41)22-43-40(47-36)44-26-12-11-21-48(23-26)20-9-5-3-4-8-19-42-34(51)24-57-31-15-10-13-27-35(31)39(54)49(38(27)53)30-17-18-33(50)46-37(30)52/h6-7,10,13-16,22,25-26,30H,3-5,8-9,11-12,17-21,23-24H2,1-2H3,(H,42,51)(H,46,50,52)(H2,43,44,45,47)/t26-,30?/m1/s1

SMILES Code: O=C(NCCCCCCCN1C[C@H](NC2=NC=C(Cl)C(NC3=CC=CC=C3S(=O)(C(C)C)=O)=N2)CCC1)COC4=CC=CC(C(N5C(CC6)C(NC6=O)=O)=O)=C4C5=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: To be determined

Shelf Life: >2 years if stored properly

Drug Formulation: To be determined

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

Product Data:

Biological target: BSJ-4-116 is a highly potent and selective CDK12 degrader (PROTAC) with an IC50 of 6 nM that downregulates DDR genes through a premature termination of transcription, primarily through increasing poly(adenylation).
In vitro activity: To assess the ability of BSJ-4-116 to inhibit the growth of drug resistant cell lines, neuroblastoma Kelly cells (KellyCDK12CF) that acquired CDK12C1039F as resistant mutation during chronic exposure to E9, a covalent kinase inhibitor directed at Cys103920, were used. Parental and CDK12C1039F Kelly cells were treated with BSJ-4-23, BSJ-4-116 or THZ531 for 6 h and 24 h, using DMSO treatment as a negative control. Moreover, antiproliferative activity of BSJ-4-116 and BSJ-4-23, but not THZ531, were also independent of the mutational status, and the degrader compounds exhibited improved GR50s in Kelly CDK12C1039F cells compared to parental cell line. Altogether, BSJ-4-116 represents a CDK12 chemical degrader with superior potency and selectivity than currently available small-molecule inhibitors. Reference: Nat Chem Biol. 2021 Jun; 17(6): 675–683. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590456/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 175.0 208.98

Preparing Stock Solutions

The following data is based on the product molecular weight 837.39 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. Jiang B, Gao Y, Che J, Lu W, Kaltheuner IH, Dries R, Kalocsay M, Berberich MJ, Jiang J, You I, Kwiatkowski N, Riching KM, Daniels DL, Sorger PK, Geyer M, Zhang T, Gray NS. Discovery and resistance mechanism of a selective CDK12 degrader. Nat Chem Biol. 2021 Jun;17(6):675-683. doi: 10.1038/s41589-021-00765-y. Epub 2021 Mar 22. PMID: 33753926; PMCID: PMC8590456.
In vitro protocol: 1. Jiang B, Gao Y, Che J, Lu W, Kaltheuner IH, Dries R, Kalocsay M, Berberich MJ, Jiang J, You I, Kwiatkowski N, Riching KM, Daniels DL, Sorger PK, Geyer M, Zhang T, Gray NS. Discovery and resistance mechanism of a selective CDK12 degrader. Nat Chem Biol. 2021 Jun;17(6):675-683. doi: 10.1038/s41589-021-00765-y. Epub 2021 Mar 22. PMID: 33753926; PMCID: PMC8590456.
In vivo protocol: TBD

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Jiang B, Gao Y, Che J, Lu W, Kaltheuner IH, Dries R, Kalocsay M, Berberich MJ, Jiang J, You I, Kwiatkowski N, Riching KM, Daniels DL, Sorger PK, Geyer M, Zhang T, Gray NS. Discovery and resistance mechanism of a selective CDK12 degrader. Nat Chem Biol. 2021 Jun;17(6):675-683. doi: 10.1038/s41589-021-00765-y. Epub 2021 Mar 22. PMID: 33753926.