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Chemical Structure| 65-49-6 Chemical Structure| 65-49-6

Structure of 4-Aminosalicylic Acid
CAS No.: 65-49-6

Chemical Structure| 65-49-6

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4-Aminosalicylic acid, known as PAS, is an antibacterial agent used to treat tuberculosis. It works by suppressing NF-κB and scavenging free radicals.

Synonyms: 4-ASA; 4-aminosalicylate; Sanipirol-4

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Product Citations

Product Citations

Pooja V. Hegde ; Michael D. Howe ; Matthew D. Zimmerman ; Helena I.M. Boshoff ; Sachin Sharma ; Brianna Remache , et al.

Abstract: Tuberculosis (TB) is one of the world's most deadly infectious diseases resulting in nearly 1.3 million deaths annually and infecting nearly one-quarter of the population. para-Aminosalicylic acid (PAS), an important second-line agent for treating drug-resistant Mycobacterium tuberculosis, has moderate bioavailability and rapid clearance that necessitate high daily doses of up to 12 g per day, which in turn causes severe gastrointestinal disturbances presumably by disruption of gut microbiota and host epithelial cells. We first synthesized a series of alkyl, acyloxy and alkyloxycarbonyloxyalkyl ester prodrugs to increase the oral bioavailability and thereby prevent intestinal accumulation as well as undesirable bioactivation by the gut microbiome to non-natural folate species that exhibit cytotoxicity. The pivoxyl prodrug of PAS was superior to all of the prodrugs examined and showed nearly quantitative absorption. While the conceptually simple prodrug approach improved the oral bioavailability of PAS, it did not address the intrinsic rapid clearance of PAS mediated by N-acetyltransferase-1 (NAT-1). Thus, we next modified the PAS scaffold to reduce NAT-1 catalyzed inactivation by introduction of groups to sterically block N-acetylation and fluorination of the aryl ring of PAS to attenuate N-acetylation by electronically deactivating the para-amino group. Among the mono-fluorinated analogs prepared, 5-fluoro-PAS, exhibited the best activity and an 11-fold decreased rate of inactivation by NAT-1 that translated to a 5-fold improved exposure as measured by area-under-the-curve (AUC) following oral dosing to CD-1 mice. The pivoxyl prodrug and fluorination at the 5-position of PAS address the primary limitations of PAS and have the potential to revitalize this second-line TB drug.

Keywords: Tuberculosis ; para-Aminosalicylic acid (PAS) ; Prodrug ; Fluorination ; Metabolism ; N-acetyltransferase

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Product Details of 4-Aminosalicylic Acid

CAS No. :65-49-6
Formula : C7H7NO3
M.W : 153.14
SMILES Code : O=C(O)C1=CC=C(N)C=C1O
Synonyms :
4-ASA; 4-aminosalicylate; Sanipirol-4
MDL No. :MFCD00007789
InChI Key :WUBBRNOQWQTFEX-UHFFFAOYSA-N
Pubchem ID :4649

Safety of 4-Aminosalicylic Acid

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H319
Precautionary Statements:P305+P351+P338

Related Pathways of 4-Aminosalicylic Acid

pyroptosis

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Human dermal fibroblast-adult (HDFa) cells 0.125–1.0 mg/mL 24 h To evaluate the cytotoxicity of the microporous hydrogel, results showed cell viability remained over 95% in the range of 0.125–1.0 mg/mL, indicating good cellular biocompatibility. Mar Drugs. 2017 Aug 16;15(8):257
RT4 cells 1-100 µM 24 h To examine the efficacy of 4-ASA, s4-ASA, and 5-ASA in alleviating pathological phenotypes induced by MPZ mutations. FACS analysis indicated that the number of apoptotic RT4 cells induced by mutant MPZ overexpression was significantly reduced following treatment with each ASA. In particular, treatment with 4-ASA reduced the levels of ER stress markers in RT4 cells induced by V169fs MPZ mutant overexpression and relieved the retention of V169fs mutant proteins in the ER. Additionally, the level of an apoptotic signal mediator (p-JNK) was only decreased in the RT4 cells expressing R98C MPZ mutant protein following treatment with 4-ASA. Int J Mol Med. 2019 Jul;44(1):125-134
Human colonic mucosal tissue 25-100 μg/ml 24 h To evaluate the effect of 4-ASA on interleukin-1 generation in human colonic mucosal tissue. Results showed that 4-ASA, at concentrations up to 100 μg/ml, did not significantly affect either interleukin-1 content or its release into the culture medium. Gut. 1992 Jul;33(7):929-32

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Sprague Dawley rats Trinitrobenzene sulphonic acid-induced colitis model Intragastric administration 50 mg/kg Daily for three weeks To evaluate the modulation of experimental colitis by 4-ASA. Results showed that 4-ASA treatment significantly reduced the extent and severity of colonic inflammation and significantly decreased colonic interleukin-1 generation. Gut. 1992 Jul;33(7):929-32

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

6.53mL

1.31mL

0.65mL

32.65mL

6.53mL

3.27mL

65.30mL

13.06mL

6.53mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
 

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