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Also known as: 1230487-00-9, Baf312 (siponimod), Mayzent, Baf-312, Siponimod [inn], Nvp-baf312-nx
Molecular Formula
C29H35F3N2O3
Molecular Weight
516.6  g/mol
InChI Key
KIHYPELVXPAIDH-HNSNBQBZSA-N
FDA UNII
RR6P8L282I

Siponimod
Siponimod is an orally bioavailable sphingosine 1-phosphate (S1P) receptor modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, siponimod targets and binds to S1P receptors 1 and 5 on lymphocytes. This prevents the egress of lymphocytes from lymph nodes, thereby reducing both the number of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues, such as the central nervous system (CNS). This prevents lymphocyte-mediated immune response and may reduce inflammation. S1P plays a key role in lymphocyte migration from lymphoid tissues. Siponimod does not target S1P receptor 3, the activation of which may be responsible for adverse effects such as bradycardia associated with other S1P receptor modulators.
1 2D Structure

Siponimod

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
1-[[4-[(E)-N-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-C-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid
2.1.2 InChI
InChI=1S/C29H35F3N2O3/c1-3-21-14-23(10-11-24(21)15-34-16-25(17-34)28(35)36)19(2)33-37-18-20-9-12-26(22-7-5-4-6-8-22)27(13-20)29(30,31)32/h9-14,22,25H,3-8,15-18H2,1-2H3,(H,35,36)/b33-19+
2.1.3 InChI Key
KIHYPELVXPAIDH-HNSNBQBZSA-N
2.1.4 Canonical SMILES
CCC1=C(C=CC(=C1)C(=NOCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)C)CN4CC(C4)C(=O)O
2.1.5 Isomeric SMILES
CCC1=C(C=CC(=C1)/C(=N/OCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)/C)CN4CC(C4)C(=O)O
2.2 Other Identifiers
2.2.1 UNII
RR6P8L282I
2.3 Synonyms
2.3.1 MeSH Synonyms

1. 1-(4-(1-((e)-4-cyclohexyl-3-trifluoromethylbenzyloxyimino)-ethyl)-2-ethylbenzyl)-azetidine-3-carboxylic Acid

2. Baf-312

3. Baf312

4. Mayzent

2.3.2 Depositor-Supplied Synonyms

1. 1230487-00-9

2. Baf312 (siponimod)

3. Mayzent

4. Baf-312

5. Siponimod [inn]

6. Nvp-baf312-nx

7. Siponimod [who-dd]

8. Baf312

9. Siponimod [usan]

10. Baf-312(siponimod)

11. 1230487-85-0

12. Rr6p8l282i

13. Chembl2336071

14. 1-((4-((1e)-1-(((4-cyclohexyl- 3-(trifluoromethyl)phenyl)methoxy)imino)ethyl)- 2-ethylphenyl)methyl)azetidine-3-carboxylic Acid

15. 3-azetidinecarboxylic Acid, 1-((4-((1e)-1-(((4-cyclohexyl-3-(trifluoromethyl)phenyl)methoxy)imino)ethyl)-2-ethylphenyl)methyl)-

16. 1-[[4-[(e)-n-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-c-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic Acid

17. Unii-rr6p8l282i

18. 3-azetidinecarboxylic Acid, 1-[[4-[(1e)-1-[[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino]ethyl]-2-ethylphenyl]methyl]-

19. J8c

20. Siponimod [mi]

21. Siponimod (usan/inn)

22. Siponimod [usan:inn]

23. Schembl641699

24. Amy595

25. Baf 312

26. Dtxsid40153847

27. C29h35f3n2o3

28. (e)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic Acid

29. 1-[[4-[(~{e})-~{n}-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-~{c}-methyl-carbonimidoyl]-2-ethyl-phenyl]methyl]azetidine-3-carboxylic Acid

30. 1-{4-[1-((e)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic Acid

31. Who 9491

32. Bdbm50428142

33. Mfcd26142651

34. Akos037645089

35. Ccg-269825

36. Cs-3876

37. Db12371

38. 1-(4-(1-((e)-4-cyclohexyl-3-trifluoromethylbenzyloxyimino)-ethyl)-2-ethylbenzyl)-azetidine-3-carboxylic Acid

39. Ac-32779

40. As-56983

41. Hy-12355

42. B3225

43. S7179

44. D11460

45. J-690082

46. (z)-4-cyano-5-((3,5-dichloropyridin-4-yl)thio)-n-(4-(methylsulfonyl)phenyl)thiophene-2-carbimidic Acid

47. 2(1h)-isoquinolinebutanoic Acid, Beta-(((4,5-dihydro-5-(2-(1h-imidazol-2-ylamino)ethyl)-3-isoxazolyl)carbonyl)amino)-3,4-dihydro-gamma-oxo-

2.4 Create Date
2010-02-01
3 Chemical and Physical Properties
Molecular Weight 516.6 g/mol
Molecular Formula C29H35F3N2O3
XLogP34.8
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count8
Rotatable Bond Count9
Exact Mass516.25997747 g/mol
Monoisotopic Mass516.25997747 g/mol
Topological Polar Surface Area62.1 Ų
Heavy Atom Count37
Formal Charge0
Complexity777
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count1
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

This drug is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults.


FDA Label


Mayzent is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.


5 Pharmacology and Biochemistry
5.1 Pharmacology

**Immune system effects** Siponimod causes a dose-dependent decrease of the peripheral blood lymphocyte count within 6 hours of the first dose, caused by the reversible accumulation of lymphocytes in lymphoid tissues, due to lack of lymphocyte release. This results in a decrease in the inflammation that is involved in multiple sclerosis. Lymphocyte counts return to normal in 90% of patients within 10 days after the cessation of therapy. **Effects on heart rate and rhythm** Siponimod causes a temporary decrease in heart rate and atrioventricular conduction upon beginning treatment. The maximum fall in heart rate is observed in the first 6 hours post ingestion. Autonomic heart responses, including diurnal variation of heart rate and response to exercise activities, are not altered by siponimod treatment. **Effects on pulmonary function** Dose-dependent decreases in absolute forced expiratory volume over a time frame of 1 second were noted in siponimod-treated patients and were higher than in patients taking placebo.


5.2 MeSH Pharmacological Classification

Sphingosine 1 Phosphate Receptor Modulators

Agents that affect the function of G-protein coupled SPHINGOSINE 1-PHOSPHATE RECEPTORS. Their binding to the receptors blocks lymphocyte migration and are often used as IMMUNOSUPPRESSANTS. (See all compounds classified as Sphingosine 1 Phosphate Receptor Modulators.)


5.3 ATC Code

L04


L - Antineoplastic and immunomodulating agents

L04 - Immunosuppressants

L04A - Immunosuppressants

L04AA - Selective immunosuppressants

L04AA42 - Siponimod


5.4 Absorption, Distribution and Excretion

Absorption

The time (Tmax) to attain maximum plasma concentrations (Cmax) after oral administration of immediate-release oral doses of siponimod was found to be approximately 4 hours ( with a range 3 - 8 hours). Siponimod is heavily absorbed (at a rate greater than or equal to 70%). The absolute oral bioavailability of siponimod is about 84%. Steady-state concentrations were attained after approximately 6 days of daily administration of a single dose of siponimod. **Effects of food on absorption** Food ingestion leads to delayed siponimod absorption (the median Tmax increased by approximately 2-3 hours). Food intake has no effect on the systemic exposure of siponimod (Cmax and AUC). Therefore, siponimod may be taken without regard to food.


Route of Elimination

Siponimod is eliminated from the systemic circulation mainly due to metabolism, and subsequent biliary/fecal excretion. Unchanged siponimod was not detected in urine.


Volume of Distribution

Siponimod distributes to body tissues with an average volume of distribution of 124 L. Siponimod fraction mesaured in plasma is 68% in humans. Animal studies demonstrate that siponimod readily crosses the blood-brain-barrier.


Clearance

Apparent systemic clearance of 3.11 L/h has been estimated in MS patients.


5.5 Metabolism/Metabolites

Siponimod is extensively metabolized, mainly by CYP2C9 enzyme (79.3%), and subsequently by CYP3A4 enzyme (18.5%). The pharmacological activity of the main metabolites M3 and M17 is not expected to be responsible for the clinical effect and the safety of siponimod in humans.


5.6 Biological Half-Life

The apparent elimination half-life is approximately 30 hours.


5.7 Mechanism of Action

Inflammation of the white and gray matter tissues in the central nervous system caused by localized immune cell infiltration and their cytokines are the initial cause of damage in MS. B lymphocytes and their cytokines are other factors in the pathogenesis of MS. Lymphotoxin [or transforming growth factor beta (TGF-)] and TNF- produced by these cells encourage inflammation. The S1P receptor is an important receptor related to the function of lymphocytes and can be found in the central nervous system. S1P receptor (S1PR) signaling is associated with a wide variety of physiological processes for lymphocytes, including their egress and recirculation. Siponimod is classified as a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds with high affinity to both S1P receptors 1 and 5. This drug blocks the ability of lymphocytes to release from the lymph nodes, decreasing the number of lymphocytes found in the peripheral blood. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is not known at this time, but may involve the abovementioned decrease of lymphocytes into the central nervous system, decreasing the inflammatory effects of MS.


API Reference Price

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10-Oct-2022
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Looking for 1230487-00-9 / Siponimod API manufacturers, exporters & distributors?

Siponimod manufacturers, exporters & distributors 1

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PharmaCompass offers a list of Siponimod API manufacturers, exporters & distributors, which can be sorted by GMP, USDMF, JDMF, KDMF, CEP (COS), WC, Price,and more, enabling you to easily find the right Siponimod manufacturer or Siponimod supplier for your needs.

Send us enquiries for free, and we will assist you in establishing a direct connection with your preferred Siponimod manufacturer or Siponimod supplier.

PharmaCompass also assists you with knowing the Siponimod API Price utilized in the formulation of products. Siponimod API Price is not always fixed or binding as the Siponimod Price is obtained through a variety of data sources. The Siponimod Price can also vary due to multiple factors, including market conditions, regulatory modifications, or negotiated pricing deals.

API | Excipient name

Siponimod

Synonyms

1230487-00-9, Baf312 (siponimod), Mayzent, Baf-312, Siponimod [inn], Nvp-baf312-nx

Cas Number

1230487-00-9

Unique Ingredient Identifier (UNII)

RR6P8L282I

About Siponimod

Siponimod is an orally bioavailable sphingosine 1-phosphate (S1P) receptor modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, siponimod targets and binds to S1P receptors 1 and 5 on lymphocytes. This prevents the egress of lymphocytes from lymph nodes, thereby reducing both the number of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues, such as the central nervous system (CNS). This prevents lymphocyte-mediated immune response and may reduce inflammation. S1P plays a key role in lymphocyte migration from lymphoid tissues. Siponimod does not target S1P receptor 3, the activation of which may be responsible for adverse effects such as bradycardia associated with other S1P receptor modulators.

Siponimod Manufacturers

A Siponimod manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Siponimod, including repackagers and relabelers. The FDA regulates Siponimod manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Siponimod API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of Siponimod manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Siponimod Suppliers

A Siponimod supplier is an individual or a company that provides Siponimod active pharmaceutical ingredient (API) or Siponimod finished formulations upon request. The Siponimod suppliers may include Siponimod API manufacturers, exporters, distributors and traders.

click here to find a list of Siponimod suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

Siponimod USDMF

A Siponimod DMF (Drug Master File) is a document detailing the whole manufacturing process of Siponimod active pharmaceutical ingredient (API) in detail. Different forms of Siponimod DMFs exist exist since differing nations have different regulations, such as Siponimod USDMF, ASMF (EDMF), JDMF, CDMF, etc.

A Siponimod DMF submitted to regulatory agencies in the US is known as a USDMF. Siponimod USDMF includes data on Siponimod's chemical properties, information on the facilities and procedures used, and details about packaging and storage. The Siponimod USDMF is kept confidential to protect the manufacturer’s intellectual property.

click here to find a list of Siponimod suppliers with USDMF on PharmaCompass.

Siponimod NDC

National Drug Code is a comprehensive database maintained by the FDA that contains information on all drugs marketed in the US. This directory includes information about finished drug products, unfinished drug products, and compounded drug products, including those containing Siponimod as an active pharmaceutical ingredient (API).

Finished drug products

The FDA updates the NDC directory daily. The NDC numbers for Siponimod API and other APIs are published in this directory by the FDA.

Unfinished drugs

The NDC unfinished drugs database includes product listing information submitted for all unfinished drugs, such as active pharmaceutical ingredients (APIs), drugs intended for further processing and bulk drug substances for compounding.

Pharmaceutical companies that manufacture Siponimod as an active pharmaceutical ingredient (API) must furnish the FDA with an updated record of all drugs that they produce, prepare, propagate, compound, or process for commercial distribution in the US at their facilities.

Compounded drug products

The NDC directory also contains data on finished compounded human drug products that contain Siponimod and are produced by outsourcing facilities. While these outsourcing facilities are not mandated to assign a Siponimod NDC to their finished compounded human drug products, they may choose to do so.

click here to find a list of Siponimod suppliers with NDC on PharmaCompass.

Siponimod GMP

Siponimod Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Siponimod GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Siponimod GMP manufacturer or Siponimod GMP API supplier for your needs.

Siponimod CoA

A Siponimod CoA (Certificate of Analysis) is a formal document that attests to Siponimod's compliance with Siponimod specifications and serves as a tool for batch-level quality control.

Siponimod CoA mostly includes findings from lab analyses of a specific batch. For each Siponimod CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Siponimod may be tested according to a variety of international standards, such as European Pharmacopoeia (Siponimod EP), Siponimod JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Siponimod USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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