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

ID: ALA4470360

PubChem CID: 146836465

Max Phase: Preclinical

Molecular Formula: C43H49N9O9

Molecular Weight: 835.92

Molecule Type: Unknown

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCOc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Standard InChI: InChI=1S/C43H49N9O9/c1-26-31-25-45-43(48-38(31)51(28-6-3-4-7-28)41(57)36(26)27(2)53)46-34-12-10-29(24-44-34)50-16-14-49(15-17-50)18-19-59-20-21-60-22-23-61-33-9-5-8-30-37(33)42(58)52(40(30)56)32-11-13-35(54)47-39(32)55/h5,8-10,12,24-25,28,32H,3-4,6-7,11,13-23H2,1-2H3,(H,47,54,55)(H,44,45,46,48)

Standard InChI Key: SFFDQTCEQLEBDF-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: Unknown	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: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 835.92	Molecular Weight (Monoisotopic): 835.3653	AlogP: 3.19	#Rotatable Bonds: 16
Polar Surface Area: 207.49	Molecular Species: NEUTRAL	HBA: 16	HBD: 2
#RO5 Violations: 2	HBA (Lipinski): 18	HBD (Lipinski): 2	#RO5 Violations (Lipinski): 2
CX Acidic pKa: 11.15	CX Basic pKa: 7.38	CX LogP: 2.75	CX LogD: 2.45
Aromatic Rings: 4	Heavy Atoms: 61	QED Weighted: 0.09	Np Likeness Score: -0.94

References

1. Rana S, Bendjennat M, Kour S, King HM, Kizhake S, Zahid M, Natarajan A.. (2019) Selective degradation of CDK6 by a palbociclib based PROTAC., 29 (11): [PMID:30935795] [10.1016/j.bmcl.2019.03.035]
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-(2-(2-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)ethoxy)ethoxy)ethoxy)-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