ID: ALA258844

Max Phase: Preclinical

Molecular Formula: C34H29N7O

Molecular Weight: 551.65

Molecule Type: Small molecule

Representations

Canonical SMILES:  O=c1[nH]c2ccccc2n1C1CCN(Cc2ccc(-c3nc4cc5[nH]cnc5cc4nc3-c3ccccc3)cc2)CC1

Standard InChI:  InChI=1S/C34H29N7O/c42-34-39-26-8-4-5-9-31(26)41(34)25-14-16-40(17-15-25)20-22-10-12-24(13-11-22)33-32(23-6-2-1-3-7-23)37-29-18-27-28(36-21-35-27)19-30(29)38-33/h1-13,18-19,21,25H,14-17,20H2,(H,35,36)(H,39,42)

Standard InChI Key:  BIWGYFZAEWGBAL-UHFFFAOYSA-N

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: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 551.65

Molecular Weight (Monoisotopic): 551.2434

AlogP: 6.32

#Rotatable Bonds: 5

Polar Surface Area: 95.49

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 11.82

CX Basic pKa: 7.65

CX LogP: 5.62

CX LogD: 5.17

Aromatic Rings: 7

Heavy Atoms: 42

QED Weighted: 0.26

Np Likeness Score: -1.02

References

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2. Lindsley CW, Zhao Z, Leister WH, Robinson RG, Barnett SF, Defeo-Jones D, Jones RE, Hartman GD, Huff JR, Huber HE, Duggan ME..  (2005)  Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors.,  15  (3): [PMID:15664853] [10.1016/j.bmcl.2004.11.011]

3. Wu Z, Robinson RG, Fu S, Barnett SF, Defeo-Jones D, Jones RE, Kral AM, Huber HE, Kohl NE, Hartman GD, Bilodeau MT..  (2008)  Rapid assembly of diverse and potent allosteric Akt inhibitors.,  18  (6): [PMID:18296048] [10.1016/j.bmcl.2007.10.023]

4. Bilodeau MT, Balitza AE, Hoffman JM, Manley PJ, Barnett SF, Defeo-Jones D, Haskell K, Jones RE, Leander K, Robinson RG, Smith AM, Huber HE, Hartman GD..  (2008)  Allosteric inhibitors of Akt1 and Akt2: a naphthyridinone with efficacy in an A2780 tumor xenograft model.,  18  (11): [PMID:18479914] [10.1016/j.bmcl.2008.04.074]

5. Zhao Z, Robinson RG, Barnett SF, Defeo-Jones D, Jones RE, Hartman GD, Huber HE, Duggan ME, Lindsley CW..  (2008)  Development of potent, allosteric dual Akt1 and Akt2 inhibitors with improved physical properties and cell activity.,  18  (1): [PMID:18054229] [10.1016/j.bmcl.2007.11.015]

6. Hu C, Solomon VR, Ulibarri G, Lee H..  (2008)  The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine.,  16  (17): [PMID:18691894] [10.1016/j.bmc.2008.07.076]

7. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P..  (2007)  The selectivity of protein kinase inhibitors: a further update.,  408  (3): [PMID:17850214] [10.1042/bj20070797]

8. Morphy R..  (2010)  Selectively nonselective kinase inhibition: striking the right balance.,  53  (4): [PMID:20166671] [10.1021/jm901132v]

9. Rodina A, Vilenchik M, Moulick K, Aguirre J, Kim J, Chiang A, Litz J, Clement CC, Kang Y, She Y, Wu N, Felts S, Wipf P, Massague J, Jiang X, Brodsky JL, Krystal GW, Chiosis G..  (2007)  Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer.,  3  (8): [PMID:17603540] [10.1038/nchembio.2007.10]

10. PubChem BioAssay data set, 

11. PubChem BioAssay data set, 

12. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ..  (2013)  A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.,  451  (2): [PMID:23398362] [10.1042/bj20121418]

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14. Desplat V, Vincenzi M, Lucas R, Moreau S, Savrimoutou S, Pinaud N, Lesbordes J, Peyrilles E, Marchivie M, Routier S, Sonnet P, Rossi F, Ronga L, Guillon J..  (2016)  Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines.,  113  [PMID:26945110] [10.1016/j.ejmech.2016.02.047]

15. Starkus JG, Poerzgen P, Layugan K, Kawabata KG, Goto JI, Suzuki S, Myers G, Kelly M, Penner R, Fleig A, Horgen FD..  (2017)  Scalaradial Is a Potent Inhibitor of Transient Receptor Potential Melastatin 2 (TRPM2) Ion Channels.,  80  (10): [PMID:29019677] [10.1021/acs.jnatprod.7b00515]

16. Zhang G, Li S, Cheng KW, Chou TF..  (2021)  AAA ATPases as therapeutic targets: Structure, functions, and small-molecule inhibitors.,  219  [PMID:33873056] [10.1016/j.ejmech.2021.113446]

17. Zhang G, Wang F, Li S, Cheng KW, Zhu Y, Huo R, Abdukirim E, Kang G, Chou TF..  (2022)  Discovery of small-molecule inhibitors of RUVBL1/2 ATPase.,  62  [PMID:35364523] [10.1016/j.bmc.2022.116726]

Source

Source(3):

• Scientific Literature
• Sanger Institute Genomics of Drug Sensitivity in Cancer
• PubChem BioAssays