ML218 | CAS# 1346233-68-8 | T-type Calcium Channel Inhibitor

MedKoo Cat#: 532192 | Name: ML218

Featured

Description:

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

ML218 is a selective inhibitor of T-type calcium channels (IC50 values are 270 and 310 nM for Cav3.3 and Cav3.2 respectively in a patch EP assay). ML218 decreases burst activity in STN neurons; reduces cataleptic behaviour in an in vivo rat model of Parkinson's disease.

Chemical Structure

ML218

CAS#1346233-68-8

Theoretical Analysis

MedKoo Cat#: 532192

Name: ML218

CAS#: 1346233-68-8

Chemical Formula: C19H26Cl2N2O

Exact Mass:

Molecular Weight: 369.33

Elemental Analysis: C, 61.79; H, 7.10; Cl, 19.20; N, 7.59; O, 4.33

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 260.00
25mg	USD 710.00

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

ML218; ML 218; ML-218 .

IUPAC/Chemical Name

3,5-dichloro-N-(((1R,5S,6s)-3-(3,3-dimethylbutyl)-3-azabicyclo[3.1.0]hexan-6-yl)methyl)benzamide

InChi Key

GSJIGYLGKSBYBC-BJWYYQGGSA-N

InChi Code

InChI=1S/C19H26Cl2N2O/c1-19(2,3)4-5-23-10-16-15(17(16)11-23)9-22-18(24)12-6-13(20)8-14(21)7-12/h6-8,15-17H,4-5,9-11H2,1-3H3,(H,22,24)/t15-,16+,17-

SMILES Code

O=C(NC[C@@H]1[C@]2([H])CN(CCC(C)(C)C)C[C@]12[H])C3=CC(Cl)=CC(Cl)=C3

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

>2 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:

ML218 is a selective inhibitor of T-type calcium channels (IC50 values are 270 and 310 nM for Cav3.3 and Cav3.2 respectively in a patch EP assay).

In vitro activity:

This study hypothesized that ML218 HCl could effectively reduce LPS-induced oral cancer cell proliferation. ML218 HCl inhibited oral cancer cell proliferation, increased apoptosis and cell death, but their efficacy was significantly reduced in the presence of bacterial antigens. ML218 HCl proved more effective than capsaicin in reducing bacterial antigen-induced Cal 27 oral cancer cell proliferation. Reference: Int J Mol Sci. 2021 Nov 22;22(22):12559. https://pubmed.ncbi.nlm.nih.gov/34830441/

In vivo activity:

By way of comparison, ML218 at doses of 1, 3, 10, and 30 mg/kg p.o. reversed cataleptic behavior in rats induced by a 0.75 mg/kg dose of haloperidol, and this is comparable to a 56.6 mg/kg p.o. dose of an A2A inhibitor (Figure 12B). Notably, the reversal with orally dosed ML218 approached the efficacy of a 56.6 mg/kg p.o. dose of the A2A inhibitor. Reference: ACS Chem Neurosci. 2011 Dec 21;2(12):730-742. https://pubmed.ncbi.nlm.nih.gov/22368764/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	125.0	338.45

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 369.33 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. Chakraborty R, Hu H, Darido C, Vickery K, Ranganathan S. ML218 HCl Is More Efficient Than Capsaicin in Inhibiting Bacterial Antigen-Induced Cal 27 Oral Cancer Cell Proliferation. Int J Mol Sci. 2021 Nov 22;22(22):12559. doi: 10.3390/ijms222212559. PMID: 34830441; PMCID: PMC8625738. 2. Li Z, Li S, Hu L, Li F, Cheung AC, Shao W, Que Y, Leung GP, Yang C. MECHANISMS UNDERLYING ACTION OF XINMAILONG INJECTION, A TRADITIONAL CHINESE MEDICINE IN CARDIAC FUNCTION IMPROVEMENT. Afr J Tradit Complement Altern Med. 2017 Jan 13;14(2):241-252. doi: 10.21010/ajtcam.v14i2.26. PMID: 28573241; PMCID: PMC5446449. 3. Devergnas A, Chen E, Ma Y, Hamada I, Pittard D, Kammermeier S, Mullin AP, Faundez V, Lindsley CW, Jones C, Smith Y, Wichmann T. Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys. J Neurophysiol. 2016 Jan 1;115(1):470-85. doi: 10.1152/jn.00858.2015. Epub 2015 Nov 4. PMID: 26538609; PMCID: PMC4760490. 4. Xiang Z, Thompson AD, Brogan JT, Schulte ML, Melancon BJ, Mi D, Lewis LM, Zou B, Yang L, Morrison R, Santomango T, Byers F, Brewer K, Aldrich JS, Yu H, Dawson ES, Li M, McManus O, Jones CK, Daniels JS, Hopkins CR, Xie XS, Conn PJ, Weaver CD, Lindsley CW. The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742. doi: 10.1021/cn200090z. PMID: 22368764; PMCID: PMC3285241.

In vitro protocol:

In vivo protocol:

1. Devergnas A, Chen E, Ma Y, Hamada I, Pittard D, Kammermeier S, Mullin AP, Faundez V, Lindsley CW, Jones C, Smith Y, Wichmann T. Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys. J Neurophysiol. 2016 Jan 1;115(1):470-85. doi: 10.1152/jn.00858.2015. Epub 2015 Nov 4. PMID: 26538609; PMCID: PMC4760490. 2. Xiang Z, Thompson AD, Brogan JT, Schulte ML, Melancon BJ, Mi D, Lewis LM, Zou B, Yang L, Morrison R, Santomango T, Byers F, Brewer K, Aldrich JS, Yu H, Dawson ES, Li M, McManus O, Jones CK, Daniels JS, Hopkins CR, Xie XS, Conn PJ, Weaver CD, Lindsley CW. The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742. doi: 10.1021/cn200090z. PMID: 22368764; PMCID: PMC3285241.

1: Li Y, Tatsui CE, Rhines LD, North RY, Harrison DS, Cassidy RM, Johansson CA, Kosturakis AK, Edwards DD, Zhang H, Dougherty PM. Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated T-type calcium channels (Cav3.2) in paclitaxel-induced peripheral neuropathy. Pain. 2017 Mar;158(3):417-429. doi: 10.1097/j.pain.0000000000000774. PubMed PMID: 27902567; PubMed Central PMCID: PMC5303135. 2: Galvan A, Devergnas A, Pittard D, Masilamoni G, Vuong J, Daniels JS, Morrison RD, Lindsley CW, Wichmann T. Lack of Antiparkinsonian Effects of Systemic Injections of the Specific T-Type Calcium Channel Blocker ML218 in MPTP-Treated Monkeys. ACS Chem Neurosci. 2016 Nov 16;7(11):1543-1551. PubMed PMID: 27596273. 3: Devergnas A, Chen E, Ma Y, Hamada I, Pittard D, Kammermeier S, Mullin AP, Faundez V, Lindsley CW, Jones C, Smith Y, Wichmann T. Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys. J Neurophysiol. 2016 Jan 1;115(1):470-85. doi: 10.1152/jn.00858.2015. PubMed PMID: 26538609; PubMed Central PMCID: PMC4760490. 4: Xie X, Brogan JT, Schulte ML, Mi D, Yu H, Dawson ES, Li M, McManus O, Engers J, Lewis LM, Thompson A, Jones CK, Weaver CD, Lindsley CW. Scaffold Hopping Affords a Highly Selective in vitro and in vivo T-Type Calcium Inhibitor Probe Free From IP Issues. 2011 Mar 31 [updated 2013 Mar 22]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK143195/ PubMed PMID: 23762962. 5: Xiang Z, Thompson AD, Brogan JT, Schulte ML, Melancon BJ, Mi D, Lewis LM, Zou B, Yang L, Morrison R, Santomango T, Byers F, Brewer K, Aldrich JS, Yu H, Dawson ES, Li M, McManus O, Jones CK, Daniels JS, Hopkins CR, Xie XS, Conn PJ, Weaver CD, Lindsley CW. The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742. PubMed PMID: 22368764; PubMed Central PMCID: PMC3285241.