N-(5-((5-tert-butyloxazol-2-yl)methylthio)thiazol-2-yl)-1-(14-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-ylamino)-2-oxo-6,9,12-trioxa-3-azatetradecyl)piperidine-4-carboxamide

ID: ALA4587232

PubChem CID: 131801483

Product Number: T422584, Order Now?

Max Phase: Preclinical

Molecular Formula: C40H52N8O10S2

Molecular Weight: 869.04

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)s2)o1

Standard InChI:  InChI=1S/C40H52N8O10S2/c1-40(2,3)29-21-43-32(58-29)24-59-33-22-44-39(60-33)46-35(51)25-9-13-47(14-10-25)23-31(50)42-12-16-56-18-20-57-19-17-55-15-11-41-27-6-4-5-26-34(27)38(54)48(37(26)53)28-7-8-30(49)45-36(28)52/h4-6,21-22,25,28,41H,7-20,23-24H2,1-3H3,(H,42,50)(H,44,46,51)(H,45,49,52)

Standard InChI Key:  BXDZOYLPNAIDOC-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 60 65  0  0  0  0  0  0  0  0999 V2000
   41.3794  -22.0385    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.3783  -22.8658    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.0931  -23.2787    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.0913  -21.6257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.8066  -22.0348    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.8115  -22.8612    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.5990  -23.1120    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   44.0809  -22.4406    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   43.5911  -21.7749    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   44.9059  -22.4357    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.8415  -20.9887    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   43.8585  -23.8951    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   45.3205  -23.1482    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   46.1419  -23.1453    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   46.5540  -22.4303    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   46.1386  -21.7164    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   45.3110  -21.7176    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   47.3790  -22.4285    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   44.8943  -21.0056    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   42.0942  -24.1036    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   41.3802  -24.5171    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.6652  -24.1055    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.9513  -24.5189    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   39.2363  -24.1073    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.5224  -24.5207    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.8074  -24.1091    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   37.0934  -24.5225    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.3785  -24.1110    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.6645  -24.5245    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.9496  -24.1129    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.2356  -24.5263    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.5207  -24.1147    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   32.8067  -24.5281    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.0918  -24.1165    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.8077  -25.3531    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   31.3778  -24.5299    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   30.6659  -24.1137    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9541  -24.5236    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9508  -25.3489    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.6657  -25.7628    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.3838  -25.3512    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.2354  -25.7596    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.5219  -25.3454    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   29.2334  -26.5846    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.7996  -26.5788    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   27.8039  -25.7591    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.0257  -25.5017    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   26.5404  -26.1622    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.0187  -26.8278    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.7154  -26.1579    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   25.2992  -26.8701    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.4742  -26.8658    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.9918  -26.2015    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   23.2061  -26.4522    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.2016  -27.2774    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.9849  -27.5363    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   22.5035  -26.0198    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.5266  -25.1952    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.7778  -26.4121    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.8658  -25.4809    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  6  2  0
  5  4  2  0
  4  1  1  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9  5  1  0
  8 10  1  0
  9 11  2  0
  7 12  2  0
 10 13  1  0
 10 17  1  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  1  0
 15 18  2  0
 17 19  2  0
  3 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 23 24  1  0
 24 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 34  1  0
 33 35  2  0
 34 36  1  0
 36 37  1  0
 36 41  1  0
 37 38  1  0
 38 39  1  0
 39 40  1  0
 40 41  1  0
 39 42  1  0
 42 43  1  0
 42 44  2  0
 43 46  1  0
 45 46  2  0
 46 47  1  0
 47 48  1  0
 48 49  2  0
 49 45  1  0
 48 50  1  0
 50 51  1  0
 51 52  1  0
 52 53  1  0
 53 54  1  0
 54 55  2  0
 55 56  1  0
 56 52  2  0
 54 57  1  0
 57 58  1  0
 57 59  1  0
 57 60  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4587232

   THAL SNS 032

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: Yes

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 869.04

Molecular Weight (Monoisotopic): 868.3248

AlogP: 3.05

#Rotatable Bonds: 21

Polar Surface Area: 223.63

Molecular Species: NEUTRAL

HBA: 16

HBD: 4

#RO5 Violations: 2

HBA (Lipinski): 18

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 7.95

CX Basic pKa: 7.11

CX LogP: 1.09

CX LogD: 1.14

Aromatic Rings: 3

Heavy Atoms: 60

QED Weighted: 0.07

Np Likeness Score: -1.41

References

1. Edmondson SD, Yang B, Fallan C..  (2019)  Proteolysis targeting chimeras (PROTACs) in 'beyond rule-of-five' chemical space: Recent progress and future challenges.,  29  (13): [PMID:31047748] [10.1016/j.bmcl.2019.04.030]

2. Wu T,Qin Z,Tian Y,Wang J,Xu C,Li Z,Bian J.  (2020)  Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update.,  63  (22): [PMID:32866383] [10.1021/acs.jmedchem.0c00744]

3. García Jiménez D, Rossi Sebastiano M, Vallaro M, Mileo V, Pizzirani D, Moretti E, Ermondi G, Caron G..  (2022)  Designing Soluble PROTACs: Strategies and Preliminary Guidelines.,  65  (19.0): [PMID:35469399] [10.1021/acs.jmedchem.2c00201]

4. Li J, Liu T, Song Y, Wang M, Liu L, Zhu H, Li Q, Lin J, Jiang H, Chen K, Zhao K, Wang M, Zhou H, Lin H, Luo C..  (2022)  Discovery of Small-Molecule Degraders of the CDK9-Cyclin T1 Complex for Targeting Transcriptional Addiction in Prostate Cancer.,  65  (16.0): [PMID:35925880] [10.1021/acs.jmedchem.2c00257]

5. Huang Z, Wang T, Wang C, Fan Y..  (2022)  CDK9 inhibitors in cancer research.,  13  (6.0): [PMID:35814933] [10.1039/d2md00040g]

6. Marak BN, Dowarah J, Khiangte L, Singh VP..  (2020)  A comprehensive insight on the recent development of Cyclic Dependent Kinase inhibitors as anticancer agents.,  203  [PMID:32707525] [10.1016/j.ejmech.2020.112571]

7. EUbOPEN.  (2023)  EUbOPEN Chemogenomics Library - Multiplex,  [10.6019/CHEMBL5303300]

8. EUbOPEN.  (2023)  EUbOPEN Chemogenomics Library - IncuCyte,  [10.6019/CHEMBL5303304]

9. EUbOPEN.  (2023)  Tm Shift (DSF) assay results for EUbOPEN Chemogenomics Library,  [10.6019/CHEMBL5308504]

10. Joshi, Kalpana S KS and 7 more authors.  2007-03  In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00.  [PMID:17363486]

11. Squires, Matthew S MS and 7 more authors.  2009-02  Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.  [PMID:19174555]

12. Goh, K C KC and 15 more authors.  2012-02  TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties.  [PMID:21860433]

13. Hole, Alison J and 9 more authors.  2013-02-14  Comparative structural and functional studies of 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity.  [PMID:23252711]

14. Cirstea, D D and 15 more authors.  2013-12  Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs.  [PMID:23807770]

15. Martin, Mathew P MP, Olesen, Sanne H SH, Georg, Gunda I GI and Schönbrunn, Ernst E.  2013-11-15  Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains.  [PMID:24007471]

16. Paiva, Cody C and 8 more authors.  2015  Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells.  [PMID:26606677]

17. Bisi, John E JE, Sorrentino, Jessica A JA, Roberts, Patrick J PJ, Tavares, Francis X FX and Strum, Jay C JC.  2016-05  Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression.  [PMID:26826116]

18. Sonawane, Yogesh A and 5 more authors.  2016-10-13  Cyclin Dependent Kinase 9 Inhibitors for Cancer Therapy.  [PMID:27171036]

19. Klaeger, Susan S and 47 more authors.  2017-12-01  The target landscape of clinical kinase drugs.  [PMID:29191878]

20. Patel, Hetal H and 15 more authors.  2018-06  ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment.  [PMID:29545334]

21. Wang, Yiting Y and 6 more authors.  2018-07-23  Design, synthesis and biological evaluation of pyrimidine derivatives as novel CDK2 inhibitors that induce apoptosis and cell cycle arrest in breast cancer cells.  [PMID:29853338]

22. Jarhad, Dnyandev B DB, Mashelkar, Karishma K KK, Kim, Hong-Rae HR, Noh, Minsoo M and Jeong, Lak Shin LS.  2018-11-21  Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) Inhibitors as Potential Therapeutics.  [PMID:29985601]

23. Ito, Masahiro M and 18 more authors.  2018-09-13  Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors.  [PMID:30067358]

24. Teng, Yuou and 10 more authors.  2019-12-01  Recent advances in the development of cyclin-dependent kinase 7 inhibitors.  [PMID:31514062]

25. Wu, Tizhi and 6 more authors.  2020-11-25  Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update.  [PMID:32866383]

26. Barlaam, Bernard and 40 more authors.  2020-12-24  Discovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies.  [PMID:33306391]

Source

Source(2):

• Scientific Literature
• EUbOPEN Chemogenomic Library