YKL-5-124 | CAS# 1957203-01-8 | CDK7 Inhibitor

MedKoo Cat#: 558735 | Name: YKL-5-124

Description:

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

YKL-5-124 is a potent and highly selective covalent CDK7 inhibitor which causes arrest at the G1/S transition and inhibition of E2F-driven gene expression. This results in no change to RNA polymerase II C-terminal domain phosphorylation.

Chemical Structure

YKL-5-124

CAS#1957203-01-8 (free base)

Theoretical Analysis

MedKoo Cat#: 558735

Name: YKL-5-124

CAS#: 1957203-01-8 (free base)

Chemical Formula: C28H33N7O3

Exact Mass: 515.2645

Molecular Weight: 515.62

Elemental Analysis: C, 65.22; H, 6.45; N, 19.02; O, 9.31

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
200mg	USD 2,250.00	Ready to ship
500mg	USD 4,250.00	Ready to ship

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Related CAS #

1957203-01-8 (free base)

Synonym

YKL5-124; YKL-5124; YKL 5-124; YKL-5 124; YKL-5-124

IUPAC/Chemical Name

(S)-3-(4-Acrylamidobenzamido)-N-(2-(dimethylamino)-1-phenylethyl)-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide

InChi Key

KPABJHHKKJIDGX-JOCHJYFZSA-N

InChi Code

InChI=1S/C28H33N7O3/c1-6-23(36)29-20-14-12-19(13-15-20)26(37)31-25-21-16-35(28(2,3)24(21)32-33-25)27(38)30-22(17-34(4)5)18-10-8-7-9-11-18/h6-15,22H,1,16-17H2,2-5H3,(H,29,36)(H,30,38)(H2,31,32,33,37)/t22-/m1/s1

SMILES Code

O=C(N(C1)C(C)(C)C2=C1C(NC(C3=CC=C(NC(C=C)=O)C=C3)=O)=NN2)N[C@@H](C4=CC=CC=C4)CN(C)C

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T21D10P19

QC Data

View QC data: current batch, Lot#T21D10P19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

CDK7 inhibitor

In vitro activity:

The discovery of a highly selective covalent CDK7 inhibitor. YKL-5-124 causes arrest at the G1/S transition and inhibition of E2F-driven gene expression; these effects are rescued by a CDK7 mutant unable to covalently engage YKL-5-124, demonstrating on-target specificity. Unlike THZ1, treatment with YKL-5-124 resulted in no change to RNA polymerase II C-terminal domain phosphorylation; however, inhibition could be reconstituted by combining YKL-5-124 and THZ531, a selective CDK12/13 inhibitor, revealing potential redundancies in CDK control of gene transcription. These findings highlight the importance of CDK7/12/13 polypharmacology for anti-cancer activity of THZ1 and posit that selective inhibition of CDK7 may be useful for treatment of cancers marked by E2F misregulation. Reference: Olson CM, Liang Y, Leggett A, Park WD, Li L, Mills CE, Elsarrag SZ, Ficarro SB, Zhang T, Düster R, Geyer M, Sim T, Marto JA, Sorger PK, Westover KD, Lin CY, Kwiatkowski N, Gray NS. Development of a Selective CDK7 Covalent Inhibitor Reveals Predominant Cell-Cycle Phenotype. Cell Chem Biol. 2019 Jun 20;26(6):792-803.e10. doi: 10.1016/j.chembiol.2019.02.012. Epub 2019 Mar 21. PMID: 30905681; PMCID: PMC6588464.

In vivo activity:

Cyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, it was demonstrated that CDK7 inhibition predominately disrupts cell-cycle progression and induces DNA replication stress and genome instability in small cell lung cancer (SCLC) while simultaneously triggering immune-response signaling. These tumor-intrinsic events provoke a robust immune surveillance program elicited by T cells, which is further enhanced by the addition of immune-checkpoint blockade. Combining YKL-5-124 with anti-PD-1 offers significant survival benefit in multiple highly aggressive murine models of SCLC, providing a rationale for new combination regimens consisting of CDK7 inhibitors and immunotherapies. Reference: Zhang H, Christensen CL, Dries R, Oser MG, Deng J, Diskin B, Li F, Pan Y, Zhang X, Yin Y, Papadopoulos E, Pyon V, Thakurdin C, Kwiatkowski N, Jani K, Rabin AR, Castro DM, Chen T, Silver H, Huang Q, Bulatovic M, Dowling CM, Sundberg B, Leggett A, Ranieri M, Han H, Li S, Yang A, Labbe KE, Almonte C, Sviderskiy VO, Quinn M, Donaghue J, Wang ES, Zhang T, He Z, Velcheti V, Hammerman PS, Freeman GJ, Bonneau R, Kaelin WG Jr, Sutherland KD, Kersbergen A, Aguirre AJ, Yuan GC, Rothenberg E, Miller G, Gray NS, Wong KK. CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer. Cancer Cell. 2020 Jan 13;37(1):37-54.e9. doi: 10.1016/j.ccell.2019.11.003. Epub 2019 Dec 26. PMID: 31883968; PMCID: PMC7277075.

Preparing Stock Solutions

The following data is based on the product molecular weight 515.62 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:

Olson CM, Liang Y, Leggett A, Park WD, Li L, Mills CE, Elsarrag SZ, Ficarro SB, Zhang T, Düster R, Geyer M, Sim T, Marto JA, Sorger PK, Westover KD, Lin CY, Kwiatkowski N, Gray NS. Development of a Selective CDK7 Covalent Inhibitor Reveals Predominant Cell-Cycle Phenotype. Cell Chem Biol. 2019 Jun 20;26(6):792-803.e10. doi: 10.1016/j.chembiol.2019.02.012. Epub 2019 Mar 21. PMID: 30905681; PMCID: PMC6588464.

In vitro protocol:

In vivo protocol:

Zhang H, Christensen CL, Dries R, Oser MG, Deng J, Diskin B, Li F, Pan Y, Zhang X, Yin Y, Papadopoulos E, Pyon V, Thakurdin C, Kwiatkowski N, Jani K, Rabin AR, Castro DM, Chen T, Silver H, Huang Q, Bulatovic M, Dowling CM, Sundberg B, Leggett A, Ranieri M, Han H, Li S, Yang A, Labbe KE, Almonte C, Sviderskiy VO, Quinn M, Donaghue J, Wang ES, Zhang T, He Z, Velcheti V, Hammerman PS, Freeman GJ, Bonneau R, Kaelin WG Jr, Sutherland KD, Kersbergen A, Aguirre AJ, Yuan GC, Rothenberg E, Miller G, Gray NS, Wong KK. CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer. Cancer Cell. 2020 Jan 13;37(1):37-54.e9. doi: 10.1016/j.ccell.2019.11.003. Epub 2019 Dec 26. PMID: 31883968; PMCID: PMC7277075.

1: Olson CM, Liang Y, Leggett A, Park WD, Li L, Mills CE, Elsarrag SZ, Ficarro SB, Zhang T, Düster R, Geyer M, Sim T, Marto JA, Sorger PK, Westover KD, Lin CY, Kwiatkowski N, Gray NS. Development of a Selective CDK7 Covalent Inhibitor Reveals Predominant Cell-Cycle Phenotype. Cell Chem Biol. 2019 Jun 20;26(6):792-803.e10. doi: 10.1016/j.chembiol.2019.02.012. Epub 2019 Mar 21. PubMed PMID: 30905681; PubMed Central PMCID: PMC6588464.