Synonym
α-Fluoromethyl-L-histidine dihydrochloride; a-FMH; alpha-FMH; (S)-alpha-Fluoromethylhistidine 2HCl; (S)-alpha-Fluoromethylhistidine HCl; (S)-alpha-Fluoromethylhistidine dihydrochloride
IUPAC/Chemical Name
(S)-2-Amino-2-(fluoromethyl)-3-(1H-imidazol-5-yl)propanoic acid dihydrochloride
InChi Key
LIJUCORJKQZTOS-XCUBXKJBSA-N
InChi Code
InChI=1S/C7H10FN3O2.2ClH/c8-3-7(9,6(12)13)1-5-2-10-4-11-5;;/h2,4H,1,3,9H2,(H,10,11)(H,12,13);2*1H/t7-;;/m1../s1
SMILES Code
O=C(O)[C@@](CF)(N)CC1=CN=CN1.[H]Cl.[H]Cl
Appearance
Solid powder (highly hydroscopic powder. It may quickly become sticky solid powder in air, which would not impact the quality).
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
alpha-FMH is a desired product with implications for the study of histidine metabolism, the examination of the effects of depleted histamine levels, and the development of novel pharmaceutical and diagnostic agents.
In vitro activity:
Addition of 10 mM PABA was observed to limit glutathione transferase activity to 33 ± 3.9% that of the uninhibited enzyme. Notably, addition of 150 μM α-FMH (alpha-Fluoromethylhistidine) (equivalent to approximately 1/70th the amount of PABA input) was sufficient to limit glutathione transferase activity to 57 ± 8.7% of the uninhibited enzyme. As micromolar concentrations of α-FMH were sufficient to significantly limit glutathione transfer activity, this study concludes that α-FMH is a potent GST inhibitor, consistent with predictions from this study’s in silico analysis.
Reference: Bioorg Med Chem Lett. 2017 Mar 15;27(6):1335-1340. https://pubmed.ncbi.nlm.nih.gov/28228363/
In vivo activity:
The results show that orexin-B significantly (p < 0.05) increased wakefulness during the infusion period and that α-FMH (alpha-Fluoromethylhistidine) significantly (p < 0.05) blocked this effect of orexin in rats. Regarding non-REM sleep, the results showed that orexin significantly decreased this sleep stage and that this orexin-B effect was blocked with prior administration of α-FMH. Fig. 2 presents further analysis regarding the total time spent during the 5-h infusion of orexin-B (10 nmol) and the influence of α-FMH on the effect of orexin-B for wakefulness [F(2,23) = 213.25, p = 0.0001], non-REM sleep [F(2,23) = 51.10, p = 0.0001], and REM sleep [F(2,23) = 19.25, p = 0.0001], respectively.
Reference: Behav Brain Res. 2010 Feb 11;207(1):151-4. https://pubmed.ncbi.nlm.nih.gov/19818811/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
260.09
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. Considine KL, Stefanidis L, Grozinger KG, Audie J, Alper BJ. Efficient synthesis of α-fluoromethylhistidine di-hydrochloride and demonstration of its efficacy as a glutathione S-transferase inhibitor. Bioorg Med Chem Lett. 2017 Mar 15;27(6):1335-1340. doi: 10.1016/j.bmcl.2017.02.024. Epub 2017 Feb 14. PMID: 28228363.
2. Yu J, Fang Q, Lou GD, Shou WT, Yue JX, Tang YY, Hou WW, Xu TL, Ohtsu H, Zhang SH, Chen Z. Histamine modulation of acute nociception involves regulation of Nav 1.8 in primary afferent neurons in mice. CNS Neurosci Ther. 2013 Sep;19(9):649-58. doi: 10.1111/cns.12134. Epub 2013 Jun 15. PMID: 23773488; PMCID: PMC6493618.
3. Yasuko S, Atanda AM, Masato M, Kazuhiko Y, Kazuki H. Alpha-fluoromethylhistidine, a histamine synthesis inhibitor, inhibits orexin-induced wakefulness in rats. Behav Brain Res. 2010 Feb 11;207(1):151-4. doi: 10.1016/j.bbr.2009.09.049. Epub 2009 Oct 8. PMID: 19818811.
In vitro protocol:
1. Considine KL, Stefanidis L, Grozinger KG, Audie J, Alper BJ. Efficient synthesis of α-fluoromethylhistidine di-hydrochloride and demonstration of its efficacy as a glutathione S-transferase inhibitor. Bioorg Med Chem Lett. 2017 Mar 15;27(6):1335-1340. doi: 10.1016/j.bmcl.2017.02.024. Epub 2017 Feb 14. PMID: 28228363.
In vivo protocol:
1. Yu J, Fang Q, Lou GD, Shou WT, Yue JX, Tang YY, Hou WW, Xu TL, Ohtsu H, Zhang SH, Chen Z. Histamine modulation of acute nociception involves regulation of Nav 1.8 in primary afferent neurons in mice. CNS Neurosci Ther. 2013 Sep;19(9):649-58. doi: 10.1111/cns.12134. Epub 2013 Jun 15. PMID: 23773488; PMCID: PMC6493618.
2. Yasuko S, Atanda AM, Masato M, Kazuhiko Y, Kazuki H. Alpha-fluoromethylhistidine, a histamine synthesis inhibitor, inhibits orexin-induced wakefulness in rats. Behav Brain Res. 2010 Feb 11;207(1):151-4. doi: 10.1016/j.bbr.2009.09.049. Epub 2009 Oct 8. PMID: 19818811.
1: Bencsáth M, Pálóczi K, Szalai C, Szenthe A, Szeberényi J, Falus A. Histidine decarboxylase in peripheral lymphocytes of healthy individuals and chronic lymphoid leukemia patients. Pathol Oncol Res. 1998;4(2):121-4. PubMed PMID: 9654597.
2: Vaziri P, Dang K, Anderson GH. Evidence for histamine involvement in the effect of histidine loads on food and water intake in rats. J Nutr. 1997 Aug;127(8):1519-26. PubMed PMID: 9237947.
3: Malmberg-Aiello P, Lamberti C, Ghelardini C, Giotti A, Bartolini A. Role of histamine in rodent antinociception. Br J Pharmacol. 1994 Apr;111(4):1269-79. PubMed PMID: 8032614; PubMed Central PMCID: PMC1910136.
4: Brandes LJ, Davie JR, Paraskevas F, Sukhu B, Bogdanovic RP, LaBella FS. The antiproliferative potency of histamine antagonists correlates with inhibition of binding of [3H]-histamine to novel intracellular receptors (HIC) in microsomal and nuclear fractions of rat liver. Agents Actions Suppl. 1991;33:325-42. PubMed PMID: 2053513.
5: Saxena SP, McNicol A, Brandes LJ, Becker AB, Gerrard JM. A role for intracellular histamine in collagen-induced platelet aggregation. Blood. 1990 Jan 15;75(2):407-14. PubMed PMID: 2104768.
6: Malmberg-Aiello P, Lamberti C, Ghelardini C, Giotti A, Bartolini A. Role of histamine in rodent antinociception. Br J Pharmacol. 1994 Apr;111(4):1269-79. doi: 10.1111/j.1476-5381.1994.tb14883.x. PMID: 8032614; PMCID: PMC1910136.
