Metarrestin | CAS# 1443414-10-5 | PNC inhibitor

MedKoo Cat#: 574793 | Name: Metarrestin

Description:

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

Metarrestin, also known as NCATS-SM0590, is a specific inhibitor of perinuclear compartment (PNC).

Chemical Structure

Metarrestin

CAS#1443414-10-5

Theoretical Analysis

MedKoo Cat#: 574793

Name: Metarrestin

CAS#: 1443414-10-5

Chemical Formula: C31H30N4O

Exact Mass: 474.2420

Molecular Weight: 474.61

Elemental Analysis: C, 78.45; H, 6.37; N, 11.81; O, 3.37

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,350.00	2 Weeks
500mg	USD 2,850.00	2 Weeks
1g	USD 4,250.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

Metarrestin; ML 246; ML-246; ML246; NCATS-SM0590; NCATS-SM-0590; NCATS-SM 0590;

IUPAC/Chemical Name

Trans-4-(7-benzyl-4-imino-5,6-diphenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl) cyclohexanol

InChi Key

WSMXAUJFLWRPNT-DIVCQZSQSA-N

InChi Code

InChI=1S/C31H30N4O/c32-30-28-27(23-12-6-2-7-13-23)29(24-14-8-3-9-15-24)34(20-22-10-4-1-5-11-22)31(28)33-21-35(30)25-16-18-26(36)19-17-25/h1-15,21,25-26,32,36H,16-20H2/t25-,26-

SMILES Code

O[C@H]1CC[C@H](N(C=NC2=C3C(C4=CC=CC=C4)=C(C5=CC=CC=C5)N2CC6=CC=CC=C6)C3=N)CC1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

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

Shelf Life

>3 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:

Metarrestin (ML246) is an orally active, first-in-class and specific perinucleolar compartment inhibitor.

In vitro activity:

Metarrestin, obtained through optimization of a screening hit, disassembles PNCs in multiple cancer cell lines, inhibits invasion in vitro, suppresses metastatic development in three mouse models of human cancer, and extends survival of mice in a metastatic pancreatic cancer xenograft model with no organ toxicity or discernable adverse effects. Metarrestin disrupts the nucleolar structure and inhibits RNA polymerase (Pol) I transcription, at least in part by interacting with the translation elongation factor eEF1A2. Reference: Sci Transl Med. 2018 May 16;10(441):eaap8307. https://pubmed.ncbi.nlm.nih.gov/29769289/

In vivo activity:

PK studies included the administration of single or multiple dose of metarrestin at 3, 10, or 25 mg/kg via intravenous (IV) injection, gavage (PO) or with chow to wild-type C57BL/6 mice and KPC mice bearing autochthonous pancreatic tumors. At 24 h after SD of 25 mg/kg PO, the intratumor concentration of metarrestin was high with a mean value of 6.2 µg/g tissue (or 13 µM), well above the cell-based IC50 of 0.4 µM. Dose-dependent normalization of FOXA1 and FOXO6 mRNA expression was observed in KPC tumors. Reference: Cancer Chemother Pharmacol. 2018 Dec;82(6):1067-1080. https://pubmed.ncbi.nlm.nih.gov/30306263/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	26.1	55.05

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 474.61 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. Kanis MJ, Qiang W, Pineda M, Maniar KP, Kim JJ. A small molecule inhibitor of the perinucleolar compartment, ML246, attenuates growth and spread of ovarian cancer. Gynecol Oncol Res Pract. 2018 Oct 2;5:7. doi: 10.1186/s40661-018-0064-2. PMID: 30305911; PMCID: PMC6167785. 2. Frankowski KJ, Wang C, Patnaik S, Schoenen FJ, Southall N, Li D, Teper Y, Sun W, Kandela I, Hu D, Dextras C, Knotts Z, Bian Y, Norton J, Titus S, Lewandowska MA, Wen Y, Farley KI, Griner LM, Sultan J, Meng Z, Zhou M, Vilimas T, Powers AS, Kozlov S, Nagashima K, Quadri HS, Fang M, Long C, Khanolkar O, Chen W, Kang J, Huang H, Chow E, Goldberg E, Feldman C, Xi R, Kim HR, Sahagian G, Baserga SJ, Mazar A, Ferrer M, Zheng W, Shilatifard A, Aubé J, Rudloff U, Marugan JJ, Huang S. Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis. Sci Transl Med. 2018 May 16;10(441):eaap8307. doi: 10.1126/scitranslmed.aap8307. PMID: 29769289; PMCID: PMC6176865. 3. Vilimas T, Wang AQ, Patnaik S, Hughes EA, Singleton MD, Knotts Z, Li D, Frankowski K, Schlomer JJ, Guerin TM, Springer S, Drennan C, Dextras C, Wang C, Gilbert D, Southall N, Ferrer M, Huang S, Kozlov S, Marugan J, Xu X, Rudloff U. Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer. Cancer Chemother Pharmacol. 2018 Dec;82(6):1067-1080. doi: 10.1007/s00280-018-3699-0. Epub 2018 Oct 10. PMID: 30306263; PMCID: PMC6267684.

In vitro protocol:

In vivo protocol:

1. Vilimas T, Wang AQ, Patnaik S, Hughes EA, Singleton MD, Knotts Z, Li D, Frankowski K, Schlomer JJ, Guerin TM, Springer S, Drennan C, Dextras C, Wang C, Gilbert D, Southall N, Ferrer M, Huang S, Kozlov S, Marugan J, Xu X, Rudloff U. Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer. Cancer Chemother Pharmacol. 2018 Dec;82(6):1067-1080. doi: 10.1007/s00280-018-3699-0. Epub 2018 Oct 10. PMID: 30306263; PMCID: PMC6267684. 2. Kanis MJ, Qiang W, Pineda M, Maniar KP, Kim JJ. A small molecule inhibitor of the perinucleolar compartment, ML246, attenuates growth and spread of ovarian cancer. Gynecol Oncol Res Pract. 2018 Oct 2;5:7. doi: 10.1186/s40661-018-0064-2. PMID: 30305911; PMCID: PMC6167785.

1. Frankowski KJ, Wang C, Patnaik S, Schoenen FJ, Southall N, Li D, Teper Y, Sun W, Kandela I, Hu D, Dextras C, Knotts Z, Bian Y, Norton J, Titus S, Lewandowska MA, Wen Y, Farley KI, Griner LM, Sultan J, Meng Z, Zhou M, Vilimas T, Powers AS, Kozlov S, Nagashima K, Quadri HS, Fang M, Long C, Khanolkar O, Chen W, Kang J, Huang H, Chow E, Goldberg E, Feldman C, Xi R, Kim HR, Sahagian G, Baserga SJ, Mazar A, Ferrer M, Zheng W, Shilatifard A, Aubé J, Rudloff U, Marugan JJ, Huang S. Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis. Sci Transl Med. 2018 May 16;10(441):eaap8307. doi: 10.1126/scitranslmed.aap8307. PMID: 29769289; PMCID: PMC6176865. 2. Vilimas T, Wang AQ, Patnaik S, Hughes EA, Singleton MD, Knotts Z, Li D, Frankowski K, Schlomer JJ, Guerin TM, Springer S, Drennan C, Dextras C, Wang C, Gilbert D, Southall N, Ferrer M, Huang S, Kozlov S, Marugan J, Xu X, Rudloff U. Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer. Cancer Chemother Pharmacol. 2018 Dec;82(6):1067-1080. doi: 10.1007/s00280-018-3699-0. Epub 2018 Oct 10. PMID: 30306263; PMCID: PMC6267684.