ID: ALA3955990
PubChem CID: 59682970
Max Phase: Preclinical
Molecular Formula: C24H22F4N6O2
Molecular Weight: 502.47
Molecule Type: Small molecule
Associated Items:
Canonical SMILES: Fc1c(O[C@H]2CC[C@](Cc3cccc(Nc4cc[nH]n4)n3)(c3nnco3)CC2)cccc1C(F)(F)F
Standard InChI: InChI=1S/C24H22F4N6O2/c25-21-17(24(26,27)28)4-2-5-18(21)36-16-7-10-23(11-8-16,22-34-30-14-35-22)13-15-3-1-6-19(31-15)32-20-9-12-29-33-20/h1-6,9,12,14,16H,7-8,10-11,13H2,(H2,29,31,32,33)/t16-,23-
Standard InChI Key: BJUHJHBPUXGUBE-QXONSOMPSA-N
Molfile:
RDKit 2D
36 40 0 0 0 0 0 0 0 0999 V2000
24.4566 -18.6914 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
24.4555 -19.5187 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
25.1703 -19.9316 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
25.8867 -19.5183 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
25.8838 -18.6878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
25.1685 -18.2786 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
26.5968 -18.2727 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
27.3128 -18.6824 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
27.3132 -19.5092 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
28.0252 -19.9189 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
28.7405 -19.5072 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
28.7394 -18.6812 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
28.0229 -18.2670 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
29.4550 -19.9197 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
29.4550 -20.7447 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
28.7404 -21.1527 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
28.7401 -21.9770 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
29.4551 -22.3903 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
30.1720 -21.9733 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
30.1687 -21.1505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
28.0254 -22.3891 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
27.3111 -21.9763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
29.4497 -19.0873 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
25.1660 -17.4537 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
23.7421 -18.2791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
27.2241 -21.1594 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
26.4172 -20.9874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
26.0044 -21.7017 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
26.5562 -22.3150 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
23.7419 -17.4541 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
23.0277 -18.6917 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
23.0248 -17.8665 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
30.2062 -19.4142 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
30.7508 -18.7957 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
30.3310 -18.0865 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
29.5268 -18.2668 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0
2 3 1 0
3 4 2 0
4 5 1 0
5 6 2 0
6 1 1 0
5 7 1 0
8 7 1 6
8 9 1 0
8 13 1 0
9 10 1 0
10 11 1 0
11 12 1 0
12 13 1 0
11 14 1 0
14 15 1 0
15 16 2 0
16 17 1 0
17 18 2 0
18 19 1 0
19 20 2 0
20 15 1 0
17 21 1 0
21 22 1 0
11 23 1 1
6 24 1 0
1 25 1 0
22 26 1 0
26 27 2 0
27 28 1 0
28 29 1 0
29 22 2 0
25 30 1 0
25 31 1 0
25 32 1 0
23 33 2 0
33 34 1 0
34 35 2 0
35 36 1 0
36 23 1 0
M END| Activity Type | Relation | Activity value | Units | Action Type | Journal | PubMed Id | doi | Assay Aladdin ID |
|---|
| Activity Type | Relation | Activity value | Units | Action Type | Journal | PubMed Id | doi | Assay Aladdin ID |
|---|
| 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 |
| MESH ID | MESH Heading | EFO IDs | EFO Terms | Max Phase for Indication | References |
|---|
| Mechanism of Action | Action Type | target ID | Target Name | Target Type | Target Organism | Binding Site Name | References |
|---|
| Molecular Weight: 502.47 | Molecular Weight (Monoisotopic): 502.1740 | AlogP: 5.59 | #Rotatable Bonds: 7 |
| Polar Surface Area: 101.75 | Molecular Species: NEUTRAL | HBA: 7 | HBD: 2 |
| #RO5 Violations: 2 | HBA (Lipinski): 8 | HBD (Lipinski): 2 | #RO5 Violations (Lipinski): 2 |
| CX Acidic pKa: 13.68 | CX Basic pKa: 4.51 | CX LogP: 4.88 | CX LogD: 4.88 |
| Aromatic Rings: 4 | Heavy Atoms: 36 | QED Weighted: 0.32 | Np Likeness Score: -0.96 |
| 1. (2008) Novel aminopyridine derivatives having aurora a selective inhibitory action, |
| 2. Fancelli, Daniele D and 24 more authors. 2006-11-30 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. [PMID:17125279] |
| 3. Yang, Jing J and 11 more authors. 2007-09-15 AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. [PMID:17495131] |
| 4. McDermott, Ultan U and 24 more authors. 2007-12-11 Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. [PMID:18077425] |
| 5. Weiss, Matthew M MM and 30 more authors. 2008-03-27 Evaluation of a series of naphthamides as potent, orally active vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors. [PMID:18324759] |
| 6. Shiotsu, Yukimasa Y and 16 more authors. 2009-08-20 KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. [PMID:19541823] |
| 7. Zarrinkar, Patrick P PP and 15 more authors. 2009-10-01 AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). [PMID:19654408] |
| 8. Shimomura, Toshiyasu T and 14 more authors. 2010-01 MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. [PMID:20053775] |
| 9. Adams, Nicholas D ND and 31 more authors. 2010-05-27 Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. [PMID:20420387] |
| 10. Bavetsias, Vassilios V and 21 more authors. 2010-07-22 Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. [PMID:20565112] |
| 11. Payton, Marc M and 20 more authors. 2010-12-01 Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. [PMID:20935223] |
| 12. Medina, Jesús R JR and 24 more authors. 2011-03-24 Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors. [PMID:21341675] |
| 13. Mollard, Alexis A and 8 more authors. 2011-12-08 Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors. [PMID:22247788] |
| 14. Lawrence, Harshani R and 14 more authors. 2012-09-13 Development of o-chlorophenyl substituted pyrimidines as exceptionally potent aurora kinase inhibitors. [PMID:22803810] |
| 15. Elkins, Jonathan M; Santaguida, Stefano; Musacchio, Andrea and Knapp, Stefan. 2012-09-13 Crystal structure of human aurora B in complex with INCENP and VX-680. [PMID:22920039] |
| 16. Glaser, Keith B KB and 22 more authors. 2012-12 Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. [PMID:22935731] |
| 17. Weïwer, Michel M and 12 more authors. 2012-12-13 A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells. [PMID:23256033] |
| 18. Li, Jie J and 6 more authors. 2013-07 A thienopyrimidine derivative induces growth inhibition and apoptosis in human cancer cell lines via inhibiting Aurora B kinase activity. [PMID:23707920] |
| 19. Shiao, Hui-Yi HY and 18 more authors. 2013-07-11 Optimization of ligand and lipophilic efficiency to identify an in vivo active furano-pyrimidine Aurora kinase inhibitor. [PMID:23808327] |
| 20. Sampson, Peter B PB and 23 more authors. 2015-01-08 The discovery of Polo-like kinase 4 inhibitors: design and optimization of spiro[cyclopropane-1,3'[3H]indol]-2'(1'H).ones as orally bioavailable antitumor agents. [PMID:24867403] |
| 21. Alder, Catherine M CM and 18 more authors. 2013-10-10 Identification of a Novel and Selective Series of Itk Inhibitors via a Template-Hopping Strategy. [PMID:24900590] |
| 22. Jagtap, Ajit Dhananjay AD and 8 more authors. 2014-10-06 Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia. [PMID:25089810] |
| 23. Carry, Jean-Christophe JC and 32 more authors. 2015-01-08 SAR156497, an exquisitely selective inhibitor of aurora kinases. [PMID:25369539] |
| 24. An, Ying Y and 7 more authors. 2016-07-01 Design and synthesis of novel benzoxazole analogs as Aurora B kinase inhibitors. [PMID:27209235] |
| 25. Klaeger, Susan S and 47 more authors. 2017-12-01 The target landscape of clinical kinase drugs. [PMID:29191878] |
| 26. Barker, Michael D MD and 11 more authors. 2018-11-15 Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. [PMID:30249354] |
| 27. Narayan, Satya S and 7 more authors. 2019-01-01 ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells. [PMID:30384048] |
| 28. Fan, Chengcheng and 7 more authors. 2020-03-15 Design, synthesis, biological evaluation of 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazolin-4(3H)-one derivatives as novel anticancer agents with Aurora kinase inhibition. [PMID:32058239] |
| 29. Lakkaniga, Naga Rajiv and 5 more authors. 2020-10-01 Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression. [PMID:32717530] |
Source(1):