Monomethylauristatin E

ID: ALA2103835

Cas Number: 474645-27-7

PubChem CID: 11542188

Product Number: M595527, Order Now?

Max Phase: Preclinical

Molecular Formula: C39H67N5O7

Molecular Weight: 717.99

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@@H](NC)C(C)C)C(C)C

Standard InChI:  InChI=1S/C39H67N5O7/c1-13-25(6)34(43(10)39(49)33(24(4)5)42-38(48)32(40-9)23(2)3)30(50-11)22-31(45)44-21-17-20-29(44)36(51-12)26(7)37(47)41-27(8)35(46)28-18-15-14-16-19-28/h14-16,18-19,23-27,29-30,32-36,40,46H,13,17,20-22H2,1-12H3,(H,41,47)(H,42,48)/t25-,26+,27+,29-,30+,32-,33-,34-,35+,36+/m0/s1

Standard InChI Key:  DASWEROEPLKSEI-UIJRFTGLSA-N

Molfile:  

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M  END

Alternative Forms

1. Parent:

   

   ALA2103835

   MMAE

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: 717.99

Molecular Weight (Monoisotopic): 717.5040

AlogP: 3.53

#Rotatable Bonds: 20

Polar Surface Area: 149.54

Molecular Species: BASE

HBA: 8

HBD: 4

#RO5 Violations: 1

HBA (Lipinski): 12

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 12.65

CX Basic pKa: 8.90

CX LogP: 3.51

CX LogD: 2.01

Aromatic Rings: 1

Heavy Atoms: 51

QED Weighted: 0.16

Np Likeness Score: 0.63

References

1. Legigan T, Clarhaut J, Renoux B, Tranoy-Opalinski I, Monvoisin A, Jayle C, Alsarraf J, Thomas M, Papot S..  (2013)  Synthesis and biological evaluations of a monomethylauristatin E glucuronide prodrug for selective cancer chemotherapy.,  67  [PMID:23845743] [10.1016/j.ejmech.2013.06.037]

2. Maderna A, Doroski M, Subramanyam C, Porte A, Leverett CA, Vetelino BC, Chen Z, Risley H, Parris K, Pandit J, Varghese AH, Shanker S, Song C, Sukuru SC, Farley KA, Wagenaar MM, Shapiro MJ, Musto S, Lam MH, Loganzo F, O'Donnell CJ..  (2014)  Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications.,  57  (24): [PMID:25431858] [10.1021/jm501649k]

3. Pettit GR, Melody N, Chapuis JC..  (2017)  Antineoplastic Agents. 603. Quinstatins: Exceptional Cancer Cell Growth Inhibitors.,  80  (3): [PMID:28211277] [10.1021/acs.jnatprod.6b01006]

4. Pettit GR, Melody N, Chapuis JC..  (2017)  Antineoplastic Agents. 604. The Path of Quinstatin Derivatives to Antibody Drug Conjugates.,  80  (9): [PMID:28895394] [10.1021/acs.jnatprod.7b00237]

5. Péresse T, Jézéquel G, Allard PM, Pham VC, Huong DTM, Blanchard F, Bignon J, Lévaique H, Wolfender JL, Litaudon M, Roussi F..  (2017)  Cytotoxic Prenylated Stilbenes Isolated from Macaranga tanarius.,  80  (10): [PMID:28972755] [10.1021/acs.jnatprod.7b00409]

6. Pettit GR, Melody N, Chapuis JC..  (2018)  Antineoplastic Agents. 605. Isoquinstatins.,  81  (3): [PMID:28926240] [10.1021/acs.jnatprod.7b00352]

7. Yokosaka S, Izawa A, Sakai C, Sakurada E, Morita Y, Nishio Y..  (2018)  Synthesis and evaluation of novel dolastatin 10 derivatives for versatile conjugations.,  26  (8): [PMID:29454703] [10.1016/j.bmc.2018.02.011]

8. White BH, Whalen K, Kriksciukaite K, Alargova R, Au Yeung T, Bazinet P, Brockman A, DuPont M, Oller H, Lemelin CA, Lim Soo P, Moreau B, Perino S, Quinn JM, Sharma G, Shinde R, Sweryda-Krawiec B, Wooster R, Bilodeau MT..  (2019)  Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo.,  62  (5): [PMID:30735385] [10.1021/acs.jmedchem.8b02036]

9. Machulkin AE, Uspenskaya AA, Zyk NU, Nimenko EA, Ber AP, Petrov SA, Polshakov VI, Shafikov RR, Skvortsov DA, Plotnikova EA, Pankratov AA, Smirnova GB, Borisova YA, Pokrovsky VS, Kolmogorov VS, Vaneev AN, Khudyakov AD, Chepikova OE, Kovalev S, Zamyatnin AA, Erofeev A, Gorelkin P, Beloglazkina EK, Zyk NV, Khazanova ES, Majouga AG..  (2021)  Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate.,  64  (23.0): [PMID:34797052] [10.1021/acs.jmedchem.1c01157]

10. Chen X, Liu F, Yu X, Li L, Yan J, Chen X, Liu Q, Liu B..  (2022)  An auristatin-based peptide-drug conjugate targeting Kita-Kyushu lung cancer antigen 1 for precision chemoradiotherapy in gastric cancer.,  241  [PMID:35932567] [10.1016/j.ejmech.2022.114617]

11. Ghosh AK, Mishevich JL, Jurica MS..  (2021)  Spliceostatins and Derivatives: Chemical Syntheses and Biological Properties of Potent Splicing Inhibitors.,  84  (5.0): [PMID:33974423] [10.1021/acs.jnatprod.1c00100]

12. Amin TU, Emara R, Pal A, Aldawod H, Jiang G, Liang D, Haque Tuhin MT, Balgoname A, Patel AD, Alhamadsheh MM..  (2022)  Enhancing the Safety and Efficacy of PSMA-Based Small-Molecule Drug Conjugates by Linker Stabilization and Conjugation to Transthyretin Binding Ligand.,  65  (22.0): [PMID:36327103] [10.1021/acs.jmedchem.2c01423]

Source

Source(1):

• Scientific Literature