N1-(3-((3-Amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N4-(4-(4-(5-(((R)-1-((2R,4S)-4-hydroxy-2-(((R)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)-pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-5-oxopentyl)-piperazin-1-yl)butyl)-succinamide

ID: ALA4639211

PubChem CID: 156013264

Max Phase: Preclinical

Molecular Formula: C56H80ClN13O6S2

Molecular Weight: 1130.93

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCN2CCN(CCCCNC(=O)CCC(=O)Nc3cccc(Sc4ncc(N5CCC(C)(N)CC5)nc4N)c3Cl)CC2)C(C)(C)C)cc1

Standard InChI:  InChI=1S/C56H80ClN13O6S2/c1-36(38-15-17-39(18-16-38)49-37(2)62-35-77-49)63-52(75)42-32-40(71)34-70(42)54(76)50(55(3,4)5)66-46(73)14-7-9-24-67-28-30-68(31-29-67)25-10-8-23-60-45(72)19-20-47(74)64-41-12-11-13-43(48(41)57)78-53-51(58)65-44(33-61-53)69-26-21-56(6,59)22-27-69/h11-13,15-18,33,35-36,40,42,50,71H,7-10,14,19-32,34,59H2,1-6H3,(H2,58,65)(H,60,72)(H,63,75)(H,64,74)(H,66,73)/t36-,40+,42-,50+/m0/s1

Standard InChI Key:  UCRQERODCAEDKT-WQFCSRJTSA-N

Molfile:  

 
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M  END

Alternative Forms

1. Parent:

   

   ALA4639211

   ---

Molecule Features

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: 1130.93

Molecular Weight (Monoisotopic): 1129.5484

AlogP: ┄

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HBA: ┄

HBD: ┄

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HBA (Lipinski): ┄

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

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CX Basic pKa: ┄

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CX LogD: ┄

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QED Weighted: ┄

Np Likeness Score: ┄

References

1. Wang M, Lu J, Wang M, Yang CY, Wang S..  (2020)  Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein.,  63  (14): [PMID:32437146] [10.1021/acs.jmedchem.0c00471]

2. Lawrence, Harshani R and 10 more authors.  2008-08-28  Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds.  [PMID:18680359]

3. Geronikaki, A A and 5 more authors.  2008-09-11  2-Thiazolylimino/heteroarylimino-5-arylidene-4-thiazolidinones as new agents with SHP-2 inhibitory action.  [PMID:18702480]

4. Dawson, Marcia I MI and 21 more authors.  2008-09-25  Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and inhibition of SRC homology 2 domain-containing protein tyrosine phosphatase-2 activity.  [PMID:18759424]

5. He, Yantao and 6 more authors.  2013-02-14  Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6-Hydroxy-benzofuran-5-carboxylic acid scaffold.  [PMID:23305444]

6. He, Yantao Y and 11 more authors.  2013-06-27  A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases.  [PMID:23713581]

7. Zeng, Li-Fan LF and 12 more authors.  2014-08-14  Therapeutic potential of targeting the oncogenic SHP2 phosphatase.  [PMID:25003231]

8. Tautz, Lutz L, Senis, Yotis A YA, Oury, Cécile C and Rahmouni, Souad S.  2015-06-15  Perspective: Tyrosine phosphatases as novel targets for antiplatelet therapy.  [PMID:25921264]

9. Sun, Wenlong W and 6 more authors.  2017-08-01  Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships.  [PMID:28642102]

10. Xie, Jingjing J and 10 more authors.  2017-12-28  Allosteric Inhibitors of SHP2 with Therapeutic Potential for Cancer Treatment.  [PMID:29155585]

11. Du, Yongli Y, Zhang, Yanhui Y, Ling, Hao H, Li, Qunyi Q and Shen, Jingkang J.  2018-01-20  Discovery of novel high potent and cellular active ADC type PTP1B inhibitors with selectivity over TC-PTP via modification interacting with C site.  [PMID:29289892]

12. Kim, Bohee and 6 more authors.  2020-01-01  Development and structure-activity relationship study of SHP2 inhibitor containing 3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulene.  [PMID:31784318]

13. Wang, Mingliang; Lu, Jianfeng; Wang, Mi; Yang, Chao-Yie and Wang, Shaomeng.  2020-07-23  Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein.  [PMID:32437146]

14. Yuan, Xinrui; Bu, Hong; Zhou, Jinpei; Yang, Chao-Yie and Zhang, Huibin.  2020-10-22  Recent Advances of SHP2 Inhibitors in Cancer Therapy: Current Development and Clinical Application.  [PMID:32460492]

Source

Source(1):

• Scientific Literature