BSJ-4-116 | CAS#2519823-34-6 | CDK12 degrader

MedKoo Cat#: 40163 | Name: BSJ-4-116

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

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
50mg	USD 850.00	2 Weeks
100mg	USD 1,450.00	2 Weeks
200mg	USD 2,250.00	2 Weeks
500mg	USD 3,650.00	2 Weeks
1g	USD 5,450.00	2 Weeks
2g	USD 9,450.00	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

More Info

Product Data

Product Data

Instruction

View handling instruction

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

	Solvent	mg/mL	mM
Solubility
	DMSO	175.0	208.98

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

In vivo protocol:

TBD

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.