MI-773 | CAS#1303607-07-9 | p53-MDM2 inhibitor

MedKoo Cat#: 206069 | Name: MI-773

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

MI-773 is a new small molecule inhibitor of the MDM2-p53 interaction, binds to MDM2 with high affinity (Ki=0.88 nM) and blocks the p53-MDM2 interaction. MI-773 is an isomer of MI-77301 (SAR405838).

Chemical Structure

MI-773

CAS#1303607-07-9

Theoretical Analysis

MedKoo Cat#: 206069

Name: MI-773

CAS#: 1303607-07-9

Chemical Formula: C29H34Cl2FN3O3

Exact Mass: 561.1961

Molecular Weight: 562.51

Elemental Analysis: C, 61.92; H, 6.09; Cl, 12.60; F, 3.38; N, 7.47; O, 8.53

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 weeks
10mg	USD 650.00	2 weeks

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Related CAS #

1303607-07-9 1303607-60-4

Synonym

MI773; MI-773; MI 773

IUPAC/Chemical Name

(2'R,3S,4'S,5'R)-6-Chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-1,2-dihydro-N-(trans-4-hydroxycyclohexyl)-2-oxospiro[3H-indole-3,3'-pyrrolidine]-5'-carboxamide

InChi Key

IDKAKZRYYDCJDU-HEVVSWJASA-N

InChi Code

InChI=1S/C29H34Cl2FN3O3/c1-28(2,3)14-22-29(19-12-7-15(30)13-21(19)34-27(29)38)23(18-5-4-6-20(31)24(18)32)25(35-22)26(37)33-16-8-10-17(36)11-9-16/h4-7,12-13,16-17,22-23,25,35-36H,8-11,14H2,1-3H3,(H,33,37)(H,34,38)/t16-,17-,22-,23+,25-,29+/m1/s1

SMILES Code

O=C([C@H](N[C@@H]1CC(C)(C)C)[C@H](C2=CC=CC(Cl)=C2F)[C@]31C(NC4=C3C=CC(Cl)=C4)=O)N[C@H]5CC[C@H](O)CC5

Appearance

Solid powder

Purity

>98%

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

MI-773 is a potent MDM2-p53 protein‐protein interaction (PPI) inhibitor with high binding affinity against MDM2 (Kd=8.2 nM).

In vitro activity:

The molecular mechanisms by which MI-773 exerted its effects were investigated using a microarray. The results showed that disturbance of the MDM2/p53 axis by MI-773 resulted in potent suppression of proliferation, induction of apoptosis and cell cycle arrest in NB cells. In addition, microarray analysis showed that MI-773 led to significant downregulation of genes involved in the G2/M phase checkpoint and upregulation of hallmark gene associated with the p53 pathway. Reference: Oncol Lett. 2021 Dec;22(6):838. https://pubmed.ncbi.nlm.nih.gov/34712362/

In vivo activity:

To evaluate the anti-tumor effect of MI-773, this study administered it to mice harboring three different patient-derived xenograft (PDX) models of ACC expressing functional p53. Single-agent MI-773 caused tumor regression in the 3 PDX models of ACC studied here. The number of p53-positive cells was increased in MI-773-treated PDX tumors (P < 0.001), with a correspondent shift in p53 localization from the nucleus to the cytoplasm. Reference: Clin Cancer Res. 2016 Jul 15;22(14):3550-9. https://pubmed.ncbi.nlm.nih.gov/26936915/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	53.0	94.22

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 562.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Vuaroqueaux V, Hendriks HR, Al-Hasani H, Peille AL, Das S, Fiebig HH. Pharmacogenomics characterization of the MDM2 inhibitor MI-773 reveals candidate tumours and predictive biomarkers. NPJ Precis Oncol. 2021 Oct 28;5(1):96. doi: 10.1038/s41698-021-00235-7. PMID: 34711913; PMCID: PMC8553758. 2. Chen YL, Zhang ZM, Li XL, Tao YF, Wu SY, Fang F, Xie Y, Liao XM, Li G, Wu D, Wang HR, Zuo R, Cao HB, Pan JJ, Yu JJ, Zhang Z, Chu XR, Zhang YP, Feng CX, Wang JW, Lu J, Hu SY, Li ZH, Pan J. MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1. Oncol Lett. 2021 Dec;22(6):838. doi: 10.3892/ol.2021.13099. Epub 2021 Oct 18. PMID: 34712362; PMCID: PMC8548782. 3. Andrews A, Warner K, Rodriguez-Ramirez C, Pearson AT, Nör F, Zhang Z, Kerk S, Kulkarni A, Helman JI, Brenner JC, Wicha MS, Wang S, Nör JE. Ablation of Cancer Stem Cells by Therapeutic Inhibition of the MDM2-p53 Interaction in Mucoepidermoid Carcinoma. Clin Cancer Res. 2019 Mar 1;25(5):1588-1600. doi: 10.1158/1078-0432.CCR-17-2730. Epub 2018 Nov 29. PMID: 30498096; PMCID: PMC6397688. 4. Warner KA, Nör F, Acasigua GA, Martins MD, Zhang Z, McLean SA, Spector ME, Chepeha DB, Helman J, Wick MJ, Moskaluk CA, Castilho RM, Pearson AT, Wang S, Nör JE. Targeting MDM2 for Treatment of Adenoid Cystic Carcinoma. Clin Cancer Res. 2016 Jul 15;22(14):3550-9. doi: 10.1158/1078-0432.CCR-15-1698. Epub 2016 Mar 2. PMID: 26936915; PMCID: PMC4947417.

In vitro protocol:

In vivo protocol:

1. Andrews A, Warner K, Rodriguez-Ramirez C, Pearson AT, Nör F, Zhang Z, Kerk S, Kulkarni A, Helman JI, Brenner JC, Wicha MS, Wang S, Nör JE. Ablation of Cancer Stem Cells by Therapeutic Inhibition of the MDM2-p53 Interaction in Mucoepidermoid Carcinoma. Clin Cancer Res. 2019 Mar 1;25(5):1588-1600. doi: 10.1158/1078-0432.CCR-17-2730. Epub 2018 Nov 29. PMID: 30498096; PMCID: PMC6397688. 2. Warner KA, Nör F, Acasigua GA, Martins MD, Zhang Z, McLean SA, Spector ME, Chepeha DB, Helman J, Wick MJ, Moskaluk CA, Castilho RM, Pearson AT, Wang S, Nör JE. Targeting MDM2 for Treatment of Adenoid Cystic Carcinoma. Clin Cancer Res. 2016 Jul 15;22(14):3550-9. doi: 10.1158/1078-0432.CCR-15-1698. Epub 2016 Mar 2. PMID: 26936915; PMCID: PMC4947417.

1: Andrews A, Warner K, Rodriguez-Ramirez C, Pearson AT, Nör F, Zhang Z, Kerk S, Kulkarni A, Helman JI, Brenner JC, Wicha MS, Wang S, Nör JE. Ablation of Cancer Stem Cells by Therapeutic Inhibition of the MDM2-p53 Interaction in Mucoepidermoid Carcinoma. Clin Cancer Res. 2019 Mar 1;25(5):1588-1600. doi: 10.1158/1078-0432.CCR-17-2730. Epub 2018 Nov 29. PubMed PMID: 30498096; PubMed Central PMCID: PMC6397688. 2: Wong JH, Alfatah M, Sin MF, Sim HM, Verma CS, Lane DP, Arumugam P. A yeast two-hybrid system for the screening and characterization of small-molecule inhibitors of protein-protein interactions identifies a novel putative Mdm2-binding site in p53. BMC Biol. 2017 Nov 9;15(1):108. doi: 10.1186/s12915-017-0446-7. PubMed PMID: 29121928; PubMed Central PMCID: PMC5680816. 3: Lu J, Guan S, Zhao Y, Yu Y, Wang Y, Shi Y, Mao X, Yang KL, Sun W, Xu X, Yi JS, Yang T, Yang J, Nuchtern JG. Novel MDM2 inhibitor SAR405838 (MI-773) induces p53-mediated apoptosis in neuroblastoma. Oncotarget. 2016 Dec 13;7(50):82757-82769. doi: 10.18632/oncotarget.12634. PubMed PMID: 27764791; PubMed Central PMCID: PMC5347730. 4: Nör F, Warner KA, Zhang Z, Acasigua GA, Pearson AT, Kerk SA, Helman JI, Sant'Ana Filho M, Wang S, Nör JE. Therapeutic Inhibition of the MDM2-p53 Interaction Prevents Recurrence of Adenoid Cystic Carcinomas. Clin Cancer Res. 2017 Feb 15;23(4):1036-1048. doi: 10.1158/1078-0432.CCR-16-1235. Epub 2016 Aug 22. PubMed PMID: 27550999; PubMed Central PMCID: PMC5315632. 5: Warner KA, Nör F, Acasigua GA, Martins MD, Zhang Z, McLean SA, Spector ME, Chepeha DB, Helman J, Wick MJ, Moskaluk CA, Castilho RM, Pearson AT, Wang S, Nör JE. Targeting MDM2 for Treatment of Adenoid Cystic Carcinoma. Clin Cancer Res. 2016 Jul 15;22(14):3550-9. doi: 10.1158/1078-0432.CCR-15-1698. Epub 2016 Mar 2. PubMed PMID: 26936915; PubMed Central PMCID: PMC4947417.