(7S,24S,27S,30S,33S,36S,39S,42S)-36-((1H-imidazol-5-yl)methyl)-27-(4-aminobutyl)-42-((S)-2-((S)-2-((S)-2-aminopropanamido)-5-guanidinopentanamido)propanamido)-7-carbamoyl-1-(2-carboxy-6-(6-hydroxy-3-oxo-3H-xanthen-9-yl)phenyl)-30-(3-guanidinopropyl)-24-(hydroxymethyl)-33-isobutyl-39-isopropyl-1,9,16,23,26,29,32,35,38,41-decaoxo-2,8,15,22,25,28,31,34,37,40-decaazapentatetracontan-45-oic acid

ID: ALA1082289

Max Phase: Preclinical

Molecular Formula: C90H134N24O23

Molecular Weight: 1920.21

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)NCCCCCC(=O)NCCCCCC(=O)N[C@@H](CCCCNC(=O)c1c(C(=O)O)cccc1-c1c2ccc(=O)cc-2oc2cc(O)ccc12)C(N)=O)C(C)C

Standard InChI:  InChI=1S/C90H134N24O23/c1-48(2)41-65(111-85(132)66(42-53-45-97-47-103-53)112-87(134)75(49(3)4)114-83(130)64(33-34-72(121)122)108-78(125)51(6)105-80(127)62(25-19-39-101-89(93)94)107-77(124)50(5)104-52(7)116)84(131)110-63(26-20-40-102-90(95)96)81(128)109-61(24-12-14-35-91)82(129)113-67(46-115)79(126)99-37-16-8-10-27-70(119)98-36-15-9-11-28-71(120)106-60(76(92)123)23-13-17-38-100-86(133)74-58(21-18-22-59(74)88(135)136)73-56-31-29-54(117)43-68(56)137-69-44-55(118)30-32-57(69)73/h18,21-22,29-32,43-45,47-51,60-67,75,115,117H,8-17,19-20,23-28,33-42,46,91H2,1-7H3,(H2,92,123)(H,97,103)(H,98,119)(H,99,126)(H,100,133)(H,104,116)(H,105,127)(H,106,120)(H,107,124)(H,108,125)(H,109,128)(H,110,131)(H,111,132)(H,112,134)(H,113,129)(H,114,130)(H,121,122)(H,135,136)(H4,93,94,101)(H4,95,96,102)/t50-,51-,60-,61-,62-,63-,64-,65-,66-,67-,75-/m0/s1

Standard InChI Key:  DUUXVEDLVMAVQN-ATJHPVBWSA-N

Molfile:  

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M  END

Alternative Forms

1. Parent:

   

   ALA1082289

   ---

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

Calculated Properties

Molecular Weight: 1920.21

Molecular Weight (Monoisotopic): 1919.0054

AlogP: ┄

#Rotatable Bonds: ┄

Polar Surface Area: ┄

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HBA: ┄

HBD: ┄

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HBA (Lipinski): ┄

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: ┄

CX LogD: ┄

Aromatic Rings: ┄

Heavy Atoms: ┄

QED Weighted: ┄

Np Likeness Score: ┄

References

1. Karatas H, Townsend EC, Bernard D, Dou Y, Wang S..  (2010)  Analysis of the binding of mixed lineage leukemia 1 (MLL1) and histone 3 peptides to WD repeat domain 5 (WDR5) for the design of inhibitors of the MLL1-WDR5 interaction.,  53  (14): [PMID:20575550] [10.1021/jm100139b]

2. Karatas, Hacer H, Townsend, Elizabeth C EC, Bernard, Denzil D, Dou, Yali Y and Wang, Shaomeng S.  2010-07-22  Analysis of the binding of mixed lineage leukemia 1 (MLL1) and histone 3 peptides to WD repeat domain 5 (WDR5) for the design of inhibitors of the MLL1-WDR5 interaction.  [PMID:20575550]

3. Bolshan, Yuri Y and 16 more authors.  2013-03-14  Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction.  [PMID:24900672]

4. Getlik, Matthäus M and 17 more authors.  2016-03-24  Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1).  [PMID:26958703]

5. Li, Dong-Dong DD and 9 more authors.  2016-08-08  Structure-based design and synthesis of small molecular inhibitors disturbing the interaction of MLL1-WDR5.  [PMID:27116709]

6. Li, Dong-Dong DD and 8 more authors.  2016-11-29  High-affinity small molecular blockers of mixed lineage leukemia 1 (MLL1)-WDR5 interaction inhibit MLL1 complex H3K4 methyltransferase activity.  [PMID:27598236]

7. Li, Dong-Dong DD and 5 more authors.  2016-11-15  Structure-based design of ester compounds to inhibit MLL complex catalytic activity by targeting mixed lineage leukemia 1 (MLL1)-WDR5 interaction.  [PMID:27720555]

8. Wang, Feng F and 17 more authors.  2018-07-12  Discovery of Potent 2-Aryl-6,7-dihydro-5 H-pyrrolo[1,2- a]imidazoles as WDR5-WIN-Site Inhibitors Using Fragment-Based Methods and Structure-Based Design.  [PMID:29889518]

9. Ye, Xiaoqing X and 11 more authors.  2019-02-15  The identification of novel small-molecule inhibitors targeting WDR5-MLL1 interaction through fluorescence polarization based high-throughput screening.  [PMID:30626558]

10. Tian, Jianhua and 24 more authors.  2020-01-23  Discovery and Structure-Based Optimization of Potent and Selective WD Repeat Domain 5 (WDR5) Inhibitors Containing a Dihydroisoquinolinone Bicyclic Core.  [PMID:31858797]

11. Chacón Simon, Selena and 14 more authors.  2020-04-23  Discovery of WD Repeat-Containing Protein 5 (WDR5)-MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design.  [PMID:32223236]

Source

Source(1):

• Scientific Literature