ID: ALA1756

Max Phase: Approved

First Approval: 1981

Molecular Formula: C23H32Cl2NO6P

Molecular Weight: 520.39

Molecule Type: Small molecule

Representations

Synonyms (4): Estramustine phosphate | Ls 299 | Ls-299 | NSC-89199
Synonyms from Alternative Forms(4):

Trade Names(1): Estracyt

Canonical SMILES:  C[C@]12CC[C@@H]3c4ccc(OC(=O)N(CCCl)CCCl)cc4CC[C@H]3[C@@H]1CC[C@@H]2OP(=O)(O)O

Standard InChI:  InChI=1S/C23H32Cl2NO6P/c1-23-9-8-18-17-5-3-16(31-22(27)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)32-33(28,29)30/h3,5,14,18-21H,2,4,6-13H2,1H3,(H2,28,29,30)/t18-,19-,20+,21+,23+/m1/s1

Standard InChI Key:  ADFOJJHRTBFFOF-RBRWEJTLSA-N

Molecule Features

Natural Product: Yes

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: Yes

Prodrug: Yes

Properties

Molecular Weight: 520.39

Molecular Weight (Monoisotopic): 519.1344

AlogP: 5.30

#Rotatable Bonds: 7

Polar Surface Area: 96.30

Molecular Species: ACID

HBA: 4

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 7

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 1.86

CX Basic pKa:

CX LogP: 4.98

CX LogD: 1.97

Aromatic Rings: 1

Heavy Atoms: 33

QED Weighted: 0.37

Np Likeness Score: 1.07

References

1. Santana L, González-Díaz H, Quezada E, Uriarte E, Yáñez M, Viña D, Orallo F..  (2008)  Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.,  51  (21): [PMID:18834112] [10.1021/jm800656v]

2. Varma MV, Obach RS, Rotter C, Miller HR, Chang G, Steyn SJ, El-Kattan A, Troutman MD..  (2010)  Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.,  53  (3): [PMID:20070106] [10.1021/jm901371v]

3. Obach RS, Lombardo F, Waters NJ..  (2008)  Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.,  36  (7): [PMID:18426954] [10.1124/dmd.108.020479]

4. Scott LM, Chen L, Daniel KG, Brooks WH, Guida WC, Lawrence HR, Sebti SM, Lawrence NJ, Wu J..  (2011)  Shp2 protein tyrosine phosphatase inhibitor activity of estramustine phosphate and its triterpenoid analogs.,  21  (2): [PMID:21193311] [10.1016/j.bmcl.2010.11.117]

5. PubChem BioAssay data set, 

6. British National Formulary (72nd edition), 

7. Unpublished dataset, 

8. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

9. Whitfield H, Hemmings AM, Mills SJ, Baker K, White G, Rushworth S, Riley AM, Potter BVL, Brearley CA..  (2021)  Allosteric Site on SHIP2 Identified Through Fluorescent Ligand Screening and Crystallography: A Potential New Target for Intervention.,  64  (7.0): [PMID:33724834] [10.1021/acs.jmedchem.0c01944]

10. Song Y, Wang S, Zhao M, Yang X, Yu B..  (2022)  Strategies Targeting Protein Tyrosine Phosphatase SHP2 for Cancer Therapy.,  65  (4.0): [PMID:35157464] [10.1021/acs.jmedchem.1c02008]

11. Sutherland JJ, Yonchev D, Fekete A, Urban L..  (2023)  A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs.,  14  (1): [PMID:37468498] [10.1038/s41467-023-40064-9]

Source

Source(5):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• British National Formulary
• Fraunhofer HDAC6