MTDIA HCl
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MedKoo CAT#: 407244

CAS#: 1399840-35-7 (HCl)

Description: MTDIA, also known as MT-DADMe-ImmA, and Methylthio-DADMe-Immucillin A, is a MTAP inhibitor. Human 5'-methylthioadenosine phosphorylase (MTAP) is solely responsible for 5'-methylthioadenosine (MTA) metabolism to permit S-adenosylmethionine salvage. Transition-state (TS) analogues of MTAP are in development as anticancer candidates. TS analogues of MTAP incorporate a cationic nitrogen and a protonated 9-deazaadenine leaving group, which are mimics of the ribocation transition state. MT-ImmA and MT-DADMe-ImmA are two examples of these TS analogues.


Chemical Structure

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MTDIA HCl
CAS# 1399840-35-7 (HCl)

Theoretical Analysis

MedKoo Cat#: 407244
Name: MTDIA HCl
CAS#: 1399840-35-7 (HCl)
Chemical Formula: C13H20ClN5OS
Exact Mass:
Molecular Weight: 329.85
Elemental Analysis: C, 47.34; H, 6.11; Cl, 10.75; N, 21.23; O, 4.85; S, 9.72

Price and Availability

Size Price Availability Quantity
5.0mg USD 150.0 Same day
10.0mg USD 250.0 Same day
25.0mg USD 450.0 Same day
50.0mg USD 850.0 Same day
100.0mg USD 1450.0 Same day
200.0mg USD 2150.0 Same day
500.0mg USD 3650.0 Same day
1.0g USD 5650.0 Same day
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Related CAS #: 1399840-35-7 (HCl)   653592-04-2 (free base)    

Synonym: MTDIA; MTDIA HCl; Methylthio-DADMe-Immucillin A; MT-DADMe-ImmA; MT-DADMe-ImmA HCl

IUPAC/Chemical Name: (3R,4S)-1-((4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-3-hydroxy-4-((methylthio)methyl)pyrrolidin-1-ium chloride

InChi Key: XQKMBJFGNRIATG-UXQCFNEQSA-N

InChi Code: InChI=1S/C13H19N5OS.ClH/c1-20-6-9-4-18(5-10(9)19)3-8-2-15-12-11(8)16-7-17-13(12)14;/h2,7,9-10,15,19H,3-6H2,1H3,(H2,14,16,17);1H/t9-,10+;/m1./s1

SMILES Code: NC(N=CN=C12)=C2NC=C1C[N+]3([H])C[C@@H]([C@H](C3)O)CSC.[Cl-]

Appearance: White to off-white 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, not in water

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

Biological target: MTDIA (MT-DADMe-ImmA) is an inhibitor of human 5'-methylthioadenosine phosphorylase (MTAP) with a Ki of 90 pM.
In vitro activity: Methylthio-DADMe-immucillin-A (MT-DADMe-ImmA, MTDIA) is an 86-pm inhibitor of human 5'-methylthioadenosine phosphorylase (MTAP). The sole function of MTAP is to recycle 5'-methylthioadenosine (MTA) to S-adenosylmethionine. Treatment of cultured cells with MT-DADMe-ImmA and MTA inhibited MTAP, increased cellular MTA concentrations, decreased polyamines, and induced apoptosis in FaDu and Cal27, two head and neck squamous cell carcinoma cell lines. The same treatment did not induce apoptosis in normal human fibroblast cell lines (CRL2522 and GM02037) or in MCF7, a breast cancer cell line with an MTAP gene deletion. MT-DADMe-ImmA alone did not induce apoptosis in any cell line, implicating MTA as the active agent. Treatment of sensitive cells caused loss of mitochondrial inner membrane potential, G(2)/M arrest, activation of mitochondria-dependent caspases, and apoptosis. Changes in cellular polyamines and MTA levels occurred in both responsive and nonresponsive cells, suggesting cell-specific epigenetic effects. A survey of aberrant DNA methylation in genomic DNA using a microarray of 12,288 CpG island clones revealed decreased CpG island methylation in treated FaDu cells compared with untreated cells. Reference: J Biol Chem. 2007 Jul 20;282(29):21477-86. https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)54836-9
In vivo activity: AdoMet recycling from 5'-methylthioadenosine (MTA) was blocked by inhibition of MTAP with methylthio-DADMe-Immucillin-A (MTDIA), an orally available, nontoxic, picomolar transition state analogue. Blood, urine, and tumor levels of MTA increased in response to MTDIA treatment. MTDIA treatment inhibited A549 (human non-small cell lung carcinoma) and H358 (human bronchioloalveolar non-small cell lung carcinoma cells) xenograft tumor growth in immunodeficient Rag2(-/-)γC(-/-) and NCr-nu mice. Systemic MTA accumulation is implicated as the tumor-suppressive metabolite because MTDIA is effective for in vivo treatment of A549 MTAP(-/-) and H358 MTAP(+/+) tumors. Tumors from treated mice showed increased MTA and decreased polyamines but little alteration in AdoMet, methionine, or adenine levels. Gene expression profiles of A549 tumors from treated and untreated mice revealed only modest alterations with 62 up-regulated and 63 down-regulated mRNAs (≥ 3-fold). MTDIA antitumor activity in xenografts supports MTAP as a target for lung cancer therapy. Reference: J Biol Chem. 2011 Feb 11;286(6):4902-11. https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)56190-5

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Soluble in DMSO, not in water 100.0 340.84

Preparing Stock Solutions

The following data is based on the product molecular weight 329.85 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.

Recalculate based on batch purity %
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. Basu I, Cordovano G, Das I, Belbin TJ, Guha C, Schramm VL. A transition state analogue of 5'-methylthioadenosine phosphorylase induces apoptosis in head and neck cancers. J Biol Chem. 2007 Jul 20;282(29):21477-86. doi: 10.1074/jbc.M702287200. Epub 2007 Jun 4. PMID: 17548352.
In vitro protocol: 1. Basu I, Cordovano G, Das I, Belbin TJ, Guha C, Schramm VL. A transition state analogue of 5'-methylthioadenosine phosphorylase induces apoptosis in head and neck cancers. J Biol Chem. 2007 Jul 20;282(29):21477-86. doi: 10.1074/jbc.M702287200. Epub 2007 Jun 4. PMID: 17548352.
In vivo protocol: 1. Basu I, Locker J, Cassera MB, Belbin TJ, Merino EF, Dong X, Hemeon I, Evans GB, Guha C, Schramm VL. Growth and metastases of human lung cancer are inhibited in mouse xenografts by a transition state analogue of 5'-methylthioadenosine phosphorylase. J Biol Chem. 2011 Feb 11;286(6):4902-11. doi: 10.1074/jbc.M110.198374. Epub 2010 Dec 6. PMID: 21135097; PMCID: PMC3039339.

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1: Evans GB, Furneaux RH, Lenz DH, Painter GF, Schramm VL, Singh V, Tyler PC. Second generation transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase. J Med Chem. 2005 Jul 14;48(14):4679-89. PubMed PMID: 16000004.

2: Tang B, Kadariya Y, Chen Y, Slifker M, Kruger WD. Expression of MTAP inhibits tumor-related phenotypes in HT1080 cells via a mechanism unrelated to its enzymatic function. G3 (Bethesda). 2014 Nov 11;5(1):35-44. doi: 10.1534/g3.114.014555. PubMed PMID: 25387827; PubMed Central PMCID: PMC4291467.

3: Wang S, Thomas K, Schramm VL. Catalytic site cooperativity in dimeric methylthioadenosine nucleosidase. Biochemistry. 2014 Mar 11;53(9):1527-35. doi: 10.1021/bi401589n. Epub 2014 Feb 21. PubMed PMID: 24502544; PubMed Central PMCID: PMC3977580.

4: Guan R, Tyler PC, Evans GB, Schramm VL. Thermodynamic analysis of transition-state features in picomolar inhibitors of human 5'-methylthioadenosine phosphorylase. Biochemistry. 2013 Nov 19;52(46):8313-22. doi: 10.1021/bi401188w. Epub 2013 Nov 8. PubMed PMID: 24148083; PubMed Central PMCID: PMC3870587.

5: Schramm VL, Gutierrez JA, Cordovano G, Basu I, Guha C, Belbin TJ, Evans GB, Tyler PC, Furneaux RH. Transition state analogues in quorum sensing and SAM recycling. Nucleic Acids Symp Ser (Oxf). 2008;(52):75-6. doi: 10.1093/nass/nrn038. PubMed PMID: 18776260; PubMed Central PMCID: PMC2725438.

6: Basu I, Cordovano G, Das I, Belbin TJ, Guha C, Schramm VL. A transition state analogue of 5'-methylthioadenosine phosphorylase induces apoptosis in head and neck cancers. J Biol Chem. 2007 Jul 20;282(29):21477-86. Epub 2007 Jun 4. PubMed PMID: 17548352.

7: Lee JE, Singh V, Evans GB, Tyler PC, Furneaux RH, Cornell KA, Riscoe MK, Schramm VL, Howell PL. Structural rationale for the affinity of pico- and femtomolar transition state analogues of Escherichia coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase. J Biol Chem. 2005 May 6;280(18):18274-82. Epub 2005 Mar 3. PubMed PMID: 15746096.



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