(2S,4S)-N-(2-((5-(4-(2,6-dimethoxy-4-(2-methyl-1-oxo-1,2-dihydro-2,7-naphthyridin-4-yl)benzyl)piperazin-1-yl)pentyl)oxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxamide

ID: ALA5271143

Max Phase: Preclinical

Molecular Formula: C53H67FN8O8S

Molecular Weight: 995.23

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: COc1cc(-c2cn(C)c(=O)c3cnccc23)cc(OC)c1CN1CCN(CCCCCOc2cc(-c3scnc3C)ccc2CNC(=O)[C@@H]2C[C@H](O)CN2C(=O)[C@@H](NC(=O)C2(F)CC2)C(C)(C)C)CC1

Standard InChI: InChI=1S/C53H67FN8O8S/c1-33-46(71-32-57-33)34-11-12-35(27-56-48(64)42-26-37(63)29-62(42)50(66)47(52(2,3)4)58-51(67)53(54)14-15-53)43(23-34)70-22-10-8-9-17-60-18-20-61(21-19-60)31-41-44(68-6)24-36(25-45(41)69-7)40-30-59(5)49(65)39-28-55-16-13-38(39)40/h11-13,16,23-25,28,30,32,37,42,47,63H,8-10,14-15,17-22,26-27,29,31H2,1-7H3,(H,56,64)(H,58,67)/t37-,42-,47+/m0/s1

Standard InChI Key: ZAGCLFXBHOXXEN-ZLGHNAGESA-N

Molfile:

 
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M  END

Associated Targets(Human)

BRD7 Tchem VHL/Bromodomain-containing protein 7 (107 Activities)

Discover Target: BRD7

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

BRD9 Tchem VHL/Bromodomain-containing protein 9 (115 Activities)

Discover Target: BRD9

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: 995.23	Molecular Weight (Monoisotopic): 994.4787	AlogP: 6.03	#Rotatable Bonds: 19
Polar Surface Area: 180.69	Molecular Species: NEUTRAL	HBA: 14	HBD: 3
#RO5 Violations: 3	HBA (Lipinski): 16	HBD (Lipinski): 3	#RO5 Violations (Lipinski): 3
CX Acidic pKa: 11.05	CX Basic pKa: 7.97	CX LogP: 3.37	CX LogD: 2.68
Aromatic Rings: 5	Heavy Atoms: 71	QED Weighted: 0.08	Np Likeness Score: -0.50

References

1. Zoppi V, Hughes SJ, Maniaci C, Testa A, Gmaschitz T, Wieshofer C, Koegl M, Riching KM, Daniels DL, Spallarossa A, Ciulli A.. (2019) Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel-Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7., 62 (2): [PMID:30540463] [10.1021/acs.jmedchem.8b01413]
2. Theodoulou, Natalie H NH and 20 more authors. 2016-02-25 Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition. [PMID:25856009]
3. Clark, Peter G K and 14 more authors. 2015-05-18 LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor. [PMID:25864491]
4. Martin, Laetitia J and 25 more authors. 2016-05-26 Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. [PMID:26914985]
5. Teuscher, Kevin B KB, Zhang, Min M and Ji, Haitao H. 2017-01-12 A Versatile Method to Determine the Cellular Bioavailability of Small-Molecule Inhibitors. [PMID:27935314]
6. Moustakim, Moses; Clark, Peter G K; Hay, Duncan A; Dixon, Darren J and Brennan, Paul E. 2016-12-07 Chemical probes and inhibitors of bromodomains outside the BET family. [PMID:29170712]

(2S,4S)-N-(2-((5-(4-(2,6-dimethoxy-4-(2-methyl-1-oxo-1,2-dihydro-2,7-naphthyridin-4-yl)benzyl)piperazin-1-yl)pentyl)oxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxamide

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Biocomponents

Calculated Properties

References

Source