Alanosine

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MedKoo CAT#: 200130

CAS#: 5854-93-3

Description: Alanosine, also known as L-alanosine, is an amino acid analogue and antibiotic derived from the bacterium Streptomyces alanosinicus with antimetabolite and potential antineoplastic activities. L-alanosine inhibits adenylosuccinate synthetase, which converts inosine monophospate (IMP) into adenylosuccinate, an intermediate in purine metabolism. L-alanosine-induced disruption of de novo purine biosynthesis is potentiated by methylthioadenosine phosphorylase (MTAP) deficiency. The clinical use of this agent may be limited by its toxicity profile. MTAP is a key enzyme in the adenine and methionine salvage pathways.

Chemical Structure

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Alanosine
CAS# 5854-93-3
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 200130
Name: Alanosine
CAS#: 5854-93-3
Chemical Formula: C3H7N3O4
Exact Mass: 149.04
Molecular Weight: 149.110
Elemental Analysis: C, 24.17; H, 4.73; N, 28.18; O, 42.92

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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Synonym: SDX102; SDX-102; SDX 102; alanosine; L-alanosine.

IUPAC/Chemical Name: (S)-2-amino-3-(hydroxy(nitroso)amino)propanoic acid

InChi Key: MLFKVJCWGUZWNV-REOHCLBHSA-N

InChi Code: InChI=1S/C3H7N3O4/c4-2(3(7)8)1-6(10)5-9/h2,10H,1,4H2,(H,7,8)/t2-/m0/s1

SMILES Code: O=C(O)[C@@H](N)CN(O)N=O

Appearance: Solid powder

Purity: >90% (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 water

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in water

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

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Product Data:
Product Data
Instruction:
View handling instruction
Biological target: Adenylosuccinate synthetase inhibitor.
In vitro activity: 2-Amino-3-(hydroxynitrosoamino)propionic acid (alanosine), at a concentration as low as 2.7 muM, completely inhibits the incorporation of hypoxanthine into adenosine triphosphate by cultured Novikoff rat hepatoma cells. Alanosine inhibits the first step in the conversion of inosine monophosphate to adenosine monophosphate because inosine monophosphate, but not adenylosuccinate, accumulates in treated cells. Alanosine treatment results in the inhibition of cell division, DNA synthesis, RNA and protein synthesis (in this order), and a depletion of the cells of adenosine triphosphate. Some of the cells accumulate in late G2 or M, but the remainder become arrested in other stages of the cell cycle. Reference: Cancer Res. 1976 Apr;36(4):1428-40. https://cancerres.aacrjournals.org/content/36/4/1428.long
In vivo activity: L-alanosine (SDX-102) exerts its cytotoxicity through inhibition of de novo purine biosynthesis, an effect potentiated by methylthioadenosine phosphorylase (MTAP) deficiency. The relevance of circadian dosing time was investigated for chronotherapeutic optimization of SDX-102. Toxicity was assessed in healthy mice following single (1,150, 1,650, or 1,850 mg/kg/d) or multiple doses (250 or 270 mg/kg/d). Efficacy was tested in mice with P388 leukemia receiving multiple doses (225 or 250 mg/kg/d). SDX-102 was administered at six circadian times 4 hours apart in mice synchronized with 12 hours of light alternating with 12 hours of darkness. MTAP expression was determined in liver, bone marrow, small intestinal mucosa, and P388 cells. Dosing at 19 hours after light onset reduced lethality 5-fold after single administration and 3-fold after multiple doses as compared with worst time [P < 0.001 and P < 0.01, respectively (chi2 test)]. Neutropenia, lymphopenia, and bone marrow hemorrhagic lesions were significantly less in mice dosed at 19 hours after light onset as compared with 7 hours after light onset. SDX-102 at 7 hours after light onset transiently ablated the 24-hour patterns in body temperature and activity. A circadian rhythm characterized small intestinal MTAP expression with a maximum at 6:30 hours after light onset (P = 0.04). A minor survival improvement was found in MTAP-deficient P388 mice receiving SDX-102 at 7 or 23 hours after light onset as compared with other times (P = 0.03, log-rank test). In conclusion, the therapeutic index of SDX-102 was improved by the delivery of SDX-102 in the mid to late activity span. Reference: Mol Cancer Ther. 2006 Feb;5(2):337-46. https://mct.aacrjournals.org/content/5/2/337.long

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Water 8.0 53.65
100 mM HCl 1.0 6.71
100 mM NaOH 1.0 6.71

Preparing Stock Solutions

The following data is based on the product molecular weight 149.11 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. Graff JC, Plagemann PG. Alanosine toxicity in Novikoff rat hepatoma cells due to inhibition of the conversion of inosine monophosphate to adenosine monophosphate. Cancer Res. 1976 Apr;36(4):1428-40. PMID: 177207. 2. Batova A, Diccianni MB, Omura-Minamisawa M, Yu J, Carrera CJ, Bridgeman LJ, Kung FH, Pullen J, Amylon MD, Yu AL. Use of alanosine as a methylthioadenosine phosphorylase-selective therapy for T-cell acute lymphoblastic leukemia in vitro. Cancer Res. 1999 Apr 1;59(7):1492-7. PMID: 10197619. 3. Li XM, Kanekal S, Crépin D, Guettier C, Carrière J, Elliott G, Lévi F. Circadian pharmacology of L-alanosine (SDX-102) in mice. Mol Cancer Ther. 2006 Feb;5(2):337-46. doi: 10.1158/1535-7163.MCT-05-0332. PMID: 16505107.
In vitro protocol: 1. Graff JC, Plagemann PG. Alanosine toxicity in Novikoff rat hepatoma cells due to inhibition of the conversion of inosine monophosphate to adenosine monophosphate. Cancer Res. 1976 Apr;36(4):1428-40. PMID: 177207. 2. Batova A, Diccianni MB, Omura-Minamisawa M, Yu J, Carrera CJ, Bridgeman LJ, Kung FH, Pullen J, Amylon MD, Yu AL. Use of alanosine as a methylthioadenosine phosphorylase-selective therapy for T-cell acute lymphoblastic leukemia in vitro. Cancer Res. 1999 Apr 1;59(7):1492-7. PMID: 10197619.
In vivo protocol: 1. Li XM, Kanekal S, Crépin D, Guettier C, Carrière J, Elliott G, Lévi F. Circadian pharmacology of L-alanosine (SDX-102) in mice. Mol Cancer Ther. 2006 Feb;5(2):337-46. doi: 10.1158/1535-7163.MCT-05-0332. PMID: 16505107.

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1: Kindler HL, Burris HA 3rd, Sandler AB, Oliff IA. A phase II multicenter study of L-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer. Invest New Drugs. 2009 Feb;27(1):75-81. doi: 10.1007/s10637-008-9160-1. Epub 2008 Jul 11. PubMed PMID: 18618081.

2: Li XM, Kanekal S, Crépin D, Guettier C, Carrière J, Elliott G, Lévi F. Circadian pharmacology of L-alanosine (SDX-102) in mice. Mol Cancer Ther. 2006 Feb;5(2):337-46. PubMed PMID: 16505107.

3: Huang J, Lipscomb WN. T-state active site of aspartate transcarbamylase: crystal structure of the carbamyl phosphate and L-alanosine ligated enzyme. Biochemistry. 2006 Jan 17;45(2):346-52. PubMed PMID: 16401065.

4: Batova A, Cottam H, Yu J, Diccianni MB, Carrera CJ, Yu AL. EFA (9-beta-D-erythrofuranosyladenine) is an effective salvage agent for methylthioadenosine phosphorylase-selective therapy of T-cell acute lymphoblastic leukemia with L-alanosine. Blood. 2006 Feb 1;107(3):898-903. Epub 2005 Oct 18. PubMed PMID: 16234352; PubMed Central PMCID: PMC1895892.

5: Li W, Su D, Mizobuchi H, Martin DS, Gu B, Gorlick R, Cole P, Bertino JR. Status of methylthioadenosine phosphorylase and its impact on cellular response to L-alanosine and methylmercaptopurine riboside in human soft tissue sarcoma cells. Oncol Res. 2004;14(7-8):373-9. PubMed PMID: 15301428.

6: Gantverg A, Elliott G, Pineault J, Demers R. Determination of derivatized l-alanosine in plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Apr 25;803(2):311-5. PubMed PMID: 15063341.

7: Efferth T, Gebhart E, Ross DD, Sauerbrey A. Identification of gene expression profiles predicting tumor cell response to L-alanosine. Biochem Pharmacol. 2003 Aug 15;66(4):613-21. PubMed PMID: 12906926.

8: Yu J. Alanosine (UCSD). Curr Opin Investig Drugs. 2001 Nov;2(11):1623-30. Review. PubMed PMID: 11763167.

9: Batova A, Diccianni MB, Omura-Minamisawa M, Yu J, Carrera CJ, Bridgeman LJ, Kung FH, Pullen J, Amylon MD, Yu AL. Use of alanosine as a methylthioadenosine phosphorylase-selective therapy for T-cell acute lymphoblastic leukemia in vitro. Cancer Res. 1999 Apr 1;59(7):1492-7. PubMed PMID: 10197619.

10: Guicherit OM, Cooper BF, Rudolph FB, Kellems RE. Amplification of an adenylosuccinate synthetase gene in alanosine-resistant murine T-lymphoma cells. Molecular cloning of a cDNA encoding the "non-muscle" isozyme. J Biol Chem. 1994 Feb 11;269(6):4488-96. PubMed PMID: 8308018.

1. Inhibiting adenine synthesis attenuates glioblastoma cell stemness and temozolomide resistance View ORCID ProfileSimranjit X. Singh, Rui Yang, Kristen Roso, Landon J. Hansen, Changzheng Du, Lee H. Chen, Paula K. Greer, Christopher J. Pirozzi, Yiping He doi: https://doi.org/10.1101/2021.06.21.449341 https://www.biorxiv.org/content/10.1101/2021.06.21.449341v1.abstract

2. Alhalabi O, Chen J, Zhang Y, Lu Y, Wang Q, Ramachandran S, Tidwell RS, Han G, Yan X, Meng J, Wang R, Hoang AG, Wang WL, Song J, Lopez L, Andreev-Drakhlin A, Siefker-Radtke A, Zhang X, Benedict WF, Shah AY, Wang J, Msaouel P, Zhang M, Guo CC, Czerniak B, Behrens C, Soto L, Papadimitrakopoulou V, Lewis J, Rinsurongkawong W, Rinsurongkawong V, Lee J, Roth J, Swisher S, Wistuba I, Heymach J, Wang J, Campbell MT, Efstathiou E, Titus M, Logothetis CJ, Ho TH, Zhang J, Wang L, Gao J. MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers. Nat Commun. 2022 Apr 4;13(1):1797. doi: 10.1038/s41467-022-29397-z. PMID: 35379845.