N1-(3-((3-Amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)-N16-((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)hexadecanediamide

ID: ALA4644736

PubChem CID: 156017854

Max Phase: Preclinical

Molecular Formula: C55H79ClN10O5S2

Molecular Weight: 1059.89

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)CCCCCCCCCCCCCCC(=O)Nc2cccc(Sc3ncc(N4CCC(C)(N)CC4)nc3N)c2Cl)C(C)(C)C)cc1

Standard InChI:  InChI=1S/C55H79ClN10O5S2/c1-36(38-24-26-39(27-25-38)48-37(2)60-35-72-48)61-51(70)42-32-40(67)34-66(42)53(71)49(54(3,4)5)64-46(69)23-18-16-14-12-10-8-7-9-11-13-15-17-22-45(68)62-41-20-19-21-43(47(41)56)73-52-50(57)63-44(33-59-52)65-30-28-55(6,58)29-31-65/h19-21,24-27,33,35-36,40,42,49,67H,7-18,22-23,28-32,34,58H2,1-6H3,(H2,57,63)(H,61,70)(H,62,68)(H,64,69)/t36-,40+,42-,49+/m0/s1

Standard InChI Key:  GCZODTDGXUMZAE-MRAFNQPSSA-N

Molfile:  

 
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M  END

Alternative Forms

1. Parent:

   

   ALA4644736

   ---

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: 1059.89

Molecular Weight (Monoisotopic): 1058.5365

AlogP: ┄

#Rotatable Bonds: ┄

Polar Surface Area: ┄

Molecular Species: ┄

HBA: ┄

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): ┄

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: ┄

CX LogD: ┄

Aromatic Rings: ┄

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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