Dinaciclib
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MedKoo CAT#: 202572

CAS#: 779353-01-4

Description: Dinaciclib, also known as SCH727965, is a potent CDK inhibitor with potential antineoplastic activity. Dinaciclib selectively inhibits cyclin dependent kinases CDK1, CDK2, CDK5, and CDK9 activity in vitro with IC(50) values of 1, 1, 3, and 4 nmol/L, respectively. Compared with flavopiridol, Dinaciclib exhibits superior activity with an improved therapeutic index. Dinaciclib induced regression of established solid tumors in a range of mouse models following intermittent scheduling of doses below the maximally tolerated level.


Chemical Structure

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Dinaciclib
CAS# 779353-01-4

Theoretical Analysis

MedKoo Cat#: 202572
Name: Dinaciclib
CAS#: 779353-01-4
Chemical Formula: C21H28N6O2
Exact Mass: 396.22737
Molecular Weight: 396.48602
Elemental Analysis: C, 63.62; H, 7.12; N, 21.20; O, 8.07

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1250.0 Ready to ship
500.0mg USD 2250.0 Ready to ship
1.0g USD 3250.0 Ready to ship
2.0g USD 5850.0 Ready to ship
5.0g USD 9650.0 2 weeks
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Synonym: SCH 727965; SCH727965; SCH-727965; PS095760; PS 095760; PS-095760; Dinaciclib.

IUPAC/Chemical Name: (S)-3-(((3-ethyl-5-(2-(2-hydroxyethyl)piperidin-1-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)pyridine 1-oxide

InChi Key: PIMQWRZWLQKKBJ-SFHVURJKSA-N

InChi Code: InChI=1S/C21H28N6O2/c1-2-17-14-23-27-19(22-13-16-6-5-9-25(29)15-16)12-20(24-21(17)27)26-10-4-3-7-18(26)8-11-28/h5-6,9,12,14-15,18,22,28H,2-4,7-8,10-11,13H2,1H3/t18-/m0/s1

SMILES Code: OCC[C@H]1N(C2=NC3=C(CC)C=NN3C(NCC4=C[N+]([O-])=CC=C4)=C2)CCCC1

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: Dinaciclib (SCH 727965) is a potent inhibitor of CDK, with IC50s of 1 nM, 1 nM, 3 nM, and 4 nM for CDK2, CDK5, CDK1, and CDK9, respectively.
In vitro activity: Here, dinaciclib caused a significant reduction in Bcl-2 expression, which, through subsequent loss of inhibition of the pro-apoptotic proteins Bax and Bak, is likely to account for Ishikawa cell death. Surprisingly, however, despite a reduction in cell proliferation, significant decreases in the expression of both Bcl-2 and Mcl-1 following dinaciclib treatment did not coincide with apoptosis in HEC-1A cells, possibly due to a compensatory effect of other anti-apoptotic proteins such as Bcl-Xl, or suggesting that other processes inhibited by dinaciclib were responsible for its effects. Reference: Cancers (Basel). 2021 Mar; 13(5): 1135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962054/
In vivo activity: To investigate the antitumor effect of dinaciclib in PDAC (pancreatic ductal adenocarcinoma), this study treated the KPC genetic mice with pancreatic tumors that measured 2-5 mm in diameter on MRI (Figure 2A). Interestingly, dinaciclib treatment significantly delayed tumor growth compared with control group (Figure 2B, 2C). In addition, this study evaluated the OS of KPC mice in different groups. Treatment with dinaciclib prolonged the OS of KPC mice from 31 to 57 days (P < 0.01 (Median)) (Figure 2D). Taken together, these results confirmed that dinaciclib can potentially elicit tumor specific antitumor immunity in KPC mice. Reference: Am J Transl Res. 2020; 12(3): 1031–1043. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137051/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 126.11
DMF 25.0 63.05
DMF:PBS (pH 7.2) (1:1) 0.5 1.26
Ethanol 32.5 81.97

Preparing Stock Solutions

The following data is based on the product molecular weight 396.48602 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. Howard D, James D, Murphy K, Garcia-Parra J, Pan-Castillo B, Rex S, Moul A, Jones E, Bilbao-Asensio M, Michue-Seijas S, Lutchman-Singh K, Margarit L, Francis LW, Rees P, Gonzalez D, Conlan RS. Dinaciclib, a Bimodal Agent Effective against Endometrial Cancer. Cancers (Basel). 2021 Mar 6;13(5):1135. doi: 10.3390/cancers13051135. PMID: 33800911; PMCID: PMC7962054. 2. Sungwan P, Lert-Itthiporn W, Silsirivanit A, Klinhom-On N, Okada S, Wongkham S, Seubwai W. Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma. PeerJ. 2021 Mar 17;9:e11067. doi: 10.7717/peerj.11067. PMID: 33777535; PMCID: PMC7980698. 3. Hur S, Kim JH, Yun J, Ju YW, Han JM, Heo W, Kim K, Jeong K, Lee HB, Han W, Noh DY, Kim JI, Moon HG. Protein Phosphatase 1H, Cyclin-Dependent Kinase Inhibitor p27, and Cyclin-Dependent Kinase 2 in Paclitaxel Resistance for Triple Negative Breast Cancers. J Breast Cancer. 2020 Mar 9;23(2):162-170. doi: 10.4048/jbc.2020.23.e20. PMID: 32395375; PMCID: PMC7192749. 4. Yang J, Hu S, Shangguan J, Eresen A, Li Y, Ma Q, Yaghmai V, Benson Iii AB, Zhang Z. Dinaciclib prolongs survival in the LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) transgenic murine models of pancreatic ductal adenocarcinoma. Am J Transl Res. 2020 Mar 15;12(3):1031-1043. PMID: 32269732; PMCID: PMC7137051.
In vitro protocol: 1. Howard D, James D, Murphy K, Garcia-Parra J, Pan-Castillo B, Rex S, Moul A, Jones E, Bilbao-Asensio M, Michue-Seijas S, Lutchman-Singh K, Margarit L, Francis LW, Rees P, Gonzalez D, Conlan RS. Dinaciclib, a Bimodal Agent Effective against Endometrial Cancer. Cancers (Basel). 2021 Mar 6;13(5):1135. doi: 10.3390/cancers13051135. PMID: 33800911; PMCID: PMC7962054. 2. Sungwan P, Lert-Itthiporn W, Silsirivanit A, Klinhom-On N, Okada S, Wongkham S, Seubwai W. Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma. PeerJ. 2021 Mar 17;9:e11067. doi: 10.7717/peerj.11067. PMID: 33777535; PMCID: PMC7980698.
In vivo protocol: 1. Hur S, Kim JH, Yun J, Ju YW, Han JM, Heo W, Kim K, Jeong K, Lee HB, Han W, Noh DY, Kim JI, Moon HG. Protein Phosphatase 1H, Cyclin-Dependent Kinase Inhibitor p27, and Cyclin-Dependent Kinase 2 in Paclitaxel Resistance for Triple Negative Breast Cancers. J Breast Cancer. 2020 Mar 9;23(2):162-170. doi: 10.4048/jbc.2020.23.e20. PMID: 32395375; PMCID: PMC7192749. 2. Yang J, Hu S, Shangguan J, Eresen A, Li Y, Ma Q, Yaghmai V, Benson Iii AB, Zhang Z. Dinaciclib prolongs survival in the LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) transgenic murine models of pancreatic ductal adenocarcinoma. Am J Transl Res. 2020 Mar 15;12(3):1031-1043. PMID: 32269732; PMCID: PMC7137051.

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1: Nemunaitis JJ, Small KA, Kirschmeier P, Zhang D, Zhu Y, Jou YM, Statkevich P, Yao SL, Bannerji R. A first-in-human, phase 1, dose-escalation study of dinaciclib, a novel cyclin-dependent kinase inhibitor, administered weekly in subjects with advanced malignancies. J Transl Med. 2013 Oct 16;11(1):259. [Epub ahead of print] PubMed PMID: 24131779; PubMed Central PMCID: PMC3853718.

2: Martin MP, Olesen SH, Georg GI, Schönbrunn E. Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem Biol. 2013 Nov 15;8(11):2360-5. doi: 10.1021/cb4003283. Epub 2013 Sep 10. PubMed PMID: 24007471; PubMed Central PMCID: PMC3846258.

3: Gojo I, Sadowska M, Walker A, Feldman EJ, Iyer SP, Baer MR, Sausville EA, Lapidus RG, Zhang D, Zhu Y, Jou YM, Poon J, Small K, Bannerji R. Clinical and laboratory studies of the novel cyclin-dependent kinase inhibitor dinaciclib (SCH 727965) in acute leukemias. Cancer Chemother Pharmacol. 2013 Oct;72(4):897-908. doi: 10.1007/s00280-013-2249-z. Epub 2013 Aug 15. PubMed PMID: 23949430; PubMed Central PMCID: PMC3784060.

4: Desai BM, Villanueva J, Nguyen TT, Lioni M, Xiao M, Kong J, Krepler C, Vultur A, Flaherty KT, Nathanson KL, Smalley KS, Herlyn M. The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling. PLoS One. 2013;8(3):e59588. doi: 10.1371/journal.pone.0059588. Epub 2013 Mar 18. PubMed PMID: 23527225; PubMed Central PMCID: PMC3601112.

5: Zhang D, Mita M, Shapiro GI, Poon J, Small K, Tzontcheva A, Kantesaria B, Zhu Y, Bannerji R, Statkevich P. Effect of aprepitant on the pharmacokinetics of the cyclin-dependent kinase inhibitor dinaciclib in patients with advanced malignancies. Cancer Chemother Pharmacol. 2012 Dec;70(6):891-8. doi: 10.1007/s00280-012-1967-y. Epub 2012 Oct 9. PubMed PMID: 23053255.

6: Johnson AJ, Yeh YY, Smith LL, Wagner AJ, Hessler J, Gupta S, Flynn J, Jones J, Zhang X, Bannerji R, Grever MR, Byrd JC. The novel cyclin-dependent kinase inhibitor dinaciclib (SCH727965) promotes apoptosis and abrogates microenvironmental cytokine protection in chronic lymphocytic leukemia cells. Leukemia. 2012 Dec;26(12):2554-7. doi: 10.1038/leu.2012.144. Epub 2012 May 30. PubMed PMID: 22791353; PubMed Central PMCID: PMC3645353.

7: Gorlick R, Kolb EA, Houghton PJ, Morton CL, Neale G, Keir ST, Carol H, Lock R, Phelps D, Kang MH, Reynolds CP, Maris JM, Billups C, Smith MA. Initial testing (stage 1) of the cyclin dependent kinase inhibitor SCH 727965 (dinaciclib) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Dec 15;59(7):1266-74. doi: 10.1002/pbc.24073. Epub 2012 Feb 7. PubMed PMID: 22315240; PubMed Central PMCID: PMC3349821.

8: Feldmann G, Mishra A, Bisht S, Karikari C, Garrido-Laguna I, Rasheed Z, Ottenhof NA, Dadon T, Alvarez H, Fendrich V, Rajeshkumar NV, Matsui W, Brossart P, Hidalgo M, Bannerji R, Maitra A, Nelkin BD. Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models. Cancer Biol Ther. 2011 Oct 1;12(7):598-609. Epub 2011 Oct 1. PubMed PMID: 21768779; PubMed Central PMCID: PMC3218385.

9: Parry D, Guzi T, Shanahan F, Davis N, Prabhavalkar D, Wiswell D, Seghezzi W, Paruch K, Dwyer MP, Doll R, Nomeir A, Windsor W, Fischmann T, Wang Y, Oft M, Chen T, Kirschmeier P, Lees EM. Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53. doi: 10.1158/1535-7163.MCT-10-0324. Epub 2010 Jul 27. PubMed PMID: 20663931.