4-((5-(4-((4-(6-((6-acetyl-8-cyclopentyl-7-hydroxy-5-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)pentyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

ID: ALA5271189

Max Phase: Preclinical

Molecular Formula: C45H53N13O6

Molecular Weight: 872.00

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: CC(=O)C1=C(O)N(C2CCCC2)c2nc(Nc3ccc(N4CCN(Cc5cn(CCCCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7=O)nn5)CC4)cn3)ncc2C1C

Standard InChI: InChI=1S/C45H53N13O6/c1-27-33-24-48-45(51-40(33)57(30-9-4-5-10-30)43(63)38(27)28(2)59)49-36-15-13-31(23-47-36)55-21-19-54(20-22-55)25-29-26-56(53-52-29)18-7-3-6-17-46-34-12-8-11-32-39(34)44(64)58(42(32)62)35-14-16-37(60)50-41(35)61/h8,11-13,15,23-24,26-27,30,35,46,63H,3-7,9-10,14,16-22,25H2,1-2H3,(H,50,60,61)(H,47,48,49,51)

Standard InChI Key: GNEQMDJHTDNIGB-UHFFFAOYSA-N

Molfile:

 
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M  END

Associated Targets(Human)

CDK4 Tclin Protein cereblon/Cyclin-dependent kinase 4 (68 Activities)

Discover Target: CDK4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CDK6 Tclin Protein cereblon/Cyclin-dependent kinase 6 (113 Activities)

Discover Target: CDK6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Natural Product: No	Oral: No	Chemical Probe: No	Parenteral: No
Molecule Type:	Topical: No	First In Class: No	Black Box: No
Chirality: No	Availability: No	Prodrug: No

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type:

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 872.00	Molecular Weight (Monoisotopic): 871.4242	AlogP: 4.44	#Rotatable Bonds: 15
Polar Surface Area: 224.01	Molecular Species: NEUTRAL	HBA: 17	HBD: 4
#RO5 Violations: 2	HBA (Lipinski): 19	HBD (Lipinski): 4	#RO5 Violations (Lipinski): 2
CX Acidic pKa: 8.96	CX Basic pKa: 5.66	CX LogP: 5.23	CX LogD: 5.21
Aromatic Rings: 4	Heavy Atoms: 64	QED Weighted: 0.10	Np Likeness Score: -1.14

References

1. Li D, Yu D, Li Y, Yang R.. (2022) A bibliometric analysis of PROTAC from 2001 to 2021., 244 [PMID:36274273] [10.1016/j.ejmech.2022.114838]
2. Gray, N S NS and 12 more authors. 1998-07-24 Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. [PMID:9677190]
3. Kubo, A A and 9 more authors. 1999-12 The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4. [PMID:10632371]
4. Soni, R R and 7 more authors. 2000-09-07 Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product. [PMID:10973815]
5. Lane, M E ME and 9 more authors. 2001-08-15 A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells. [PMID:11507069]
6. Tavares, Francis X FX and 7 more authors. 2004-09-09 N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy. [PMID:15341487]
7. Fry, David W DW and 10 more authors. 2004-11 Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. [PMID:15542782]
8. Pennati, Marzia M and 12 more authors. 2005-09 Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation. [PMID:16170024]
9. Sridhar, Jayalakshmi J, Akula, Nagaraju N and Pattabiraman, Nagarajan N. 2006-03-24 Selectivity and potency of cyclin-dependent kinase inhibitors. [PMID:16584130]
10. DePinto, Wanda W and 19 more authors. 2006-11 In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. [PMID:17121911]
11. Joshi, Kalpana S KS and 7 more authors. 2007-03 In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00. [PMID:17363486]
12. Squires, Matthew S MS and 7 more authors. 2009-02 Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. [PMID:19174555]
13. Cirstea, D D and 15 more authors. 2013-12 Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. [PMID:23807770]
14. Gelbert, Lawrence M LM and 16 more authors. 2014-10 Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. [PMID:24919854]
15. Paiva, Cody C and 8 more authors. 2015 Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. [PMID:26606677]
16. Bisi, John E JE, Sorrentino, Jessica A JA, Roberts, Patrick J PJ, Tavares, Francis X FX and Strum, Jay C JC. 2016-05 Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. [PMID:26826116]
17. Klaeger, Susan S and 47 more authors. 2017-12-01 The target landscape of clinical kinase drugs. [PMID:29191878]
18. Wang, Yan Y and 10 more authors. 2018-03-01 Design and synthesis of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine as a highly potent and selective cyclin-dependent kinases 4 and 6 inhibitors and the discovery of structure-activity relationships. [PMID:29429832]
19. Tear, Westley F and 16 more authors. 2020-01-23 Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis. [PMID:31846577]
20. Wu, Tizhi and 6 more authors. 2020-11-25 Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update. [PMID:32866383]

4-((5-(4-((4-(6-((6-acetyl-8-cyclopentyl-7-hydroxy-5-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)pentyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Biocomponents

Calculated Properties

References

Source