2-(5-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-4-methoxy-5H-pyrrol-2-yl)-1H-indole

ID: ALA408194

Chembl Id: CHEMBL408194

Max Phase: Phase

Molecular Formula: C20H19N3O

Molecular Weight: 317.39

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Obatoclax | GX15-070

Synonyms from Alternative Forms(5): Obatoclax | Obatoclax mesilate | Obatoclax mesylate | GX-15-070MS | GX15-070MS

Canonical SMILES:  COC1=CC(c2cc3ccccc3[nH]2)=N/C1=C\c1[nH]c(C)cc1C

Standard InChI:  InChI=1S/C20H19N3O/c1-12-8-13(2)21-16(12)10-19-20(24-3)11-18(23-19)17-9-14-6-4-5-7-15(14)22-17/h4-11,21-22H,1-3H3/b19-10-

Standard InChI Key:  RFTSSZJZXOSICM-GRSHGNNSSA-N

Alternative Forms

1. Parent:

   

   ALA408194

   OBATOCLAX

2. Alternative Forms:

   

   ALA408194

   OBATOCLAX MESYLATE

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 317.39

Molecular Weight (Monoisotopic): 317.1528

AlogP: 4.49

#Rotatable Bonds: 3

Polar Surface Area: 53.17

Molecular Species: NEUTRAL

HBA: 2

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 13.97

CX Basic pKa: 4.68

CX LogP: 3.14

CX LogD: 3.14

Aromatic Rings: 3

Heavy Atoms: 24

QED Weighted: 0.73

Np Likeness Score: -0.15

References

1. Nguyen M, Marcellus RC, Roulston A, Watson M, Serfass L, Murthy Madiraju SR, Goulet D, Viallet J, Bélec L, Billot X, Acoca S, Purisima E, Wiegmans A, Cluse L, Johnstone RW, Beauparlant P, Shore GC..  (2007)  Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis.,  104  (49): [PMID:18040043] [10.1073/pnas.0709443104]

2. Papireddy K, Smilkstein M, Kelly JX, Shweta, Salem SM, Alhamadsheh M, Haynes SW, Challis GL, Reynolds KA..  (2011)  Antimalarial activity of natural and synthetic prodiginines.,  54  (15): [PMID:21736388] [10.1021/jm200543y]

3. Saugues E, Debaud AL, Anizon F, Bonnefoy N, Moreau P..  (2012)  Synthesis and biological activities of polyquinoline derivatives: new Bcl-2 family protein modulators.,  57  [PMID:23047228] [10.1016/j.ejmech.2012.09.012]

4. Su JC, Chen KF, Chen WL, Liu CY, Huang JW, Tai WT, Chen PJ, Kim I, Shiau CW..  (2012)  Synthesis and biological activity of obatoclax derivatives as novel and potent SHP-1 agonists.,  56  [PMID:22982119] [10.1016/j.ejmech.2012.08.024]

5. Unpublished dataset, 

6. Unpublished dataset, 

7. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]

8. Nhu D, Lessene G, Huang DCS, Burns CJ.  (2016)  Small molecules targeting Mcl-1: the search for a silver bullet in cancer therapy,  7  (5): [10.1039/C5MD00582E]

9. Wan Y, Dai N, Tang Z, Fang H..  (2018)  Small-molecule Mcl-1 inhibitors: Emerging anti-tumor agents.,  146  [PMID:29407973] [10.1016/j.ejmech.2018.01.076]

10. Unpublished dataset, 

11. Patil S, Ghosh D, Radhakrishna M, Basu S..  (2020)  Mitochondrial Impairment by Cyanine-Based Small Molecules Induces Apoptosis in Cancer Cells.,  11  (1): [PMID:31938458] [10.1021/acsmedchemlett.9b00304]

12. Yang S, Mao Y, Zhang H, Xu Y, An J, Huang Z..  (2019)  The chemical biology of apoptosis: Revisited after 17 years.,  177  [PMID:31129454] [10.1016/j.ejmech.2019.05.019]

Source

Source(4):

• Scientific Literature
• Clinical Candidates
• Gene Expression Atlas Compounds
• AstraZeneca Deposited Data