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Also known as: 1257044-40-8, Abt-199, Venclexta, Gdc-0199, Abt199, Abt 199
Molecular Formula
C45H50ClN7O7S
Molecular Weight
868.4  g/mol
InChI Key
LQBVNQSMGBZMKD-UHFFFAOYSA-N
FDA UNII
N54AIC43PW

Venetoclax
Venetoclax is an orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia.
Venetoclax is a BCL-2 Inhibitor. The mechanism of action of venetoclax is as a P-Glycoprotein Inhibitor. The physiologic effect of venetoclax is by means of Increased Cellular Death.
1 2D Structure

Venetoclax

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
2.1.2 InChI
InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)
2.1.3 InChI Key
LQBVNQSMGBZMKD-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC1(CCC(=C(C1)C2=CC=C(C=C2)Cl)CN3CCN(CC3)C4=CC(=C(C=C4)C(=O)NS(=O)(=O)C5=CC(=C(C=C5)NCC6CCOCC6)[N+](=O)[O-])OC7=CN=C8C(=C7)C=CN8)C
2.2 Other Identifiers
2.2.1 UNII
N54AIC43PW
2.3 Synonyms
2.3.1 MeSH Synonyms

1. 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-n-((3-nitro-4-((tetrahydro-2h-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1h-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide

2. Abt-199

3. Benzamide, 4-(4-((2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl)methyl)-1-piperazinyl)-n-((3-nitro-4-(((tetrahydro-2h-pyran-4-yl)methyl)amino)phenyl)sulfonyl)-2-(1h-pyrrolo(2,3-b)pyridin-5-yloxy)-

4. Gdc-0199

5. Rg-7601

6. Rg7601

7. Venclexta

2.3.2 Depositor-Supplied Synonyms

1. 1257044-40-8

2. Abt-199

3. Venclexta

4. Gdc-0199

5. Abt199

6. Abt 199

7. Rg7601

8. Venetoclax (abt199)

9. Gdc 0199

10. Rg-7601

11. Venetoclax; Abt-199

12. 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

13. Venetoclax (abt-199)

14. N54aic43pw

15. Abt-199 (gdc-0199)

16. 2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)-n-(3-nitro-4-((tetrahydro-2h-pyran-4-yl)methy

17. 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-n-((3-nitro-4-((tetrahydro-2h-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1h-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide

18. 4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-n-[[3-nitro-4-[[(tetrahydro-2h-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)-benzamide

19. Benzamide, 4-(4-((2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl)methyl)-1-piperazinyl)-n-((3-nitro-4-(((tetrahydro-2h-pyran-4-yl)methyl)amino)phenyl)sulfonyl)-2-(1h-pyrrolo(2,3-b)pyridin-5-yloxy)-

20. Venclyxto

21. Bdbm189459

22. Unii-n54aic43pw

23. 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-n-({3-nitro-4-[(oxan-4-ylmethyl)amino]benzene}sulfonyl)-2-{1h-pyrrolo[2,3-b]pyridin-5-yloxy}benzamide

24. 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-n-({3-nitro-4-[(tetrahydro-2h-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

25. 4-{4-[(4'-chloro-5,5-dimethyl[3,4,5,6-tetrahydro[1,1'-biphenyl]]-2-yl)methyl]piperazin-1-yl}-n-(3-nitro-4-{[(oxan-4-yl)methyl]amino}benzene-1-sulfonyl)-2-[(1h-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide

26. Venetoclax [usan:inn]

27. Venclexta (tn)

28. Benzamide, 4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-n-[[3-nitro-4-[[(tetrahydro-2h-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)-

29. Venetoclax [mi]

30. Venetoclax(abt-199)

31. Venetoclax [inn]

32. Venetoclax [jan]

33. Venetoclax [usan]

34. Venetoclax [who-dd]

35. Mls006010298

36. Schembl523816

37. Venetoclax (jan/usan/inn)

38. Amy343

39. Gtpl8318

40. Chembl3137309

41. Schembl19236295

42. Venetoclax [orange Book]

43. Bdbm60828

44. Dtxsid30154863

45. Ex-a168

46. Chebi:133021

47. Hms3653j06

48. Hms3745e07

49. Bcp06811

50. Bdbm50162774

51. Mfcd23160052

52. Nsc766270

53. Akos025289539

54. Zinc150338755

55. Ccg-270543

56. Cs-1155

57. Db11581

58. Ks-1470

59. Nsc-766270

60. Sb16499

61. Ncgc00345789-01

62. Ncgc00345789-05

63. Ncgc00345789-10

64. Ncgc00345789-11

65. Ac-28754

66. Da-35360

67. Hy-15531

68. Smr004701366

69. Ft-0699586

70. S8048

71. Sw219672-1

72. J3.516.625d

73. D10679

74. Us9174982, 5

75. A850921

76. Us9174982, 369

77. J-005269

78. Q23671272

79. 2-((1h-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-n-((3-nitro-4-(((tetrahydro-2h-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide

80. 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-n-((3-nitro-4-((tetrahydro-2hpyran-4-ylmethyl) Amino)phenyl)sulfonyl)-2-(1h-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide

81. 4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-n-[[3-nitro-4-[[(tetrahydro-2h-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

82. 4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-cyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(tetrahydropyran-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

83. 4-{4-[(4'-chloro-5,5-dimethyl[3,4,5,6-tetrahydro[1,1'-biphenyl]]-2-yl)methyl]piperazin-1-yl}-n-[(3-nitro-4-{[(oxan-4-yl

2.4 Create Date
2011-01-31
3 Chemical and Physical Properties
Molecular Weight 868.4 g/mol
Molecular Formula C45H50ClN7O7S
XLogP38.2
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count11
Rotatable Bond Count12
Exact Mass867.3180958 g/mol
Monoisotopic Mass867.3180958 g/mol
Topological Polar Surface Area183 Ų
Heavy Atom Count61
Formal Charge0
Complexity1640
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

A BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.


FDA Label


Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (see section 5. 1).

Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy.

Venclyxto monotherapy is indicated for the treatment of CLL:

- in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B cell receptor pathway inhibitor, or

- in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

Venclyxto in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Venetoclax induces rapid and potent onset apoptosis of CLL cells, powerful enough to act within 24h and to lead to tumor lysis syndrome,,. Selective targeting of BCL2 with venetoclax has demonstrated a manageable safety profile and has been shown to induce significant response in patients with relapsed CLL (chronic lymphocytic leukemia) or SLL (small lymphocytic leukemia), including patients with poor prognostic features. This drug is not expected to have a significant impact on the cardiac QT interval. Venetoclax has demonstrated efficacy in various types of lymphoid malignancies, including relapsed/ refractory CLL harboring deletion 17p, with an overall response rate of approximately 80%.


5.2 MeSH Pharmacological Classification

Antineoplastic Agents

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
VENETOCLAX
5.3.2 FDA UNII
N54AIC43PW
5.3.3 Pharmacological Classes
Increased Cellular Death [PE]; P-Glycoprotein Inhibitors [MoA]; BCL-2 Inhibitor [EPC]
5.4 ATC Code

L01XX52


L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01X - Other antineoplastic agents

L01XX - Other antineoplastic agents

L01XX52 - Venetoclax


5.5 Absorption, Distribution and Excretion

Absorption

Following several oral administrations after a meal, the maximum plasma concentration of venetoclax was reached 5-8 hours after the dose. Venetoclax steady state AUC (area under the curve) increased proportionally over the dose range of 150-800 mg. After a low-fat meal, venetoclax mean ( standard deviation) steady-state Cmax was 2.1 1.1 g/mL and AUC0-24 was 32.8 16.9 gh/mL at the 400 mg once daily dose. When compared with the fasted state, venetoclax exposure increased by 3.4 times when ingested with a low-fat meal and 5.2 times with a high-fat meal. When comparing low versus high fat, the Cmax and AUC were both increased by 50% when ingested with a high-fat meal. The FDA label indicataes that venetoclax should be taken with food,.


Route of Elimination

After single oral administration of 200 mg radiolabeled [14C]-venetoclax dose to healthy subjects, >99.9% of the dose was found in feces and <0.1% of the dose was excreted in urine within 9 days, suggesting that hepatic elimination is responsible for the clearance of venetoclax from systemic circulation. Unchanged venetoclax accounted for 20.8% of the radioactive dose excreted in feces.


Volume of Distribution

The population estimate for apparent volume of distribution (Vdss/F) of venetoclax ranged from 256-321 L.


Clearance

Mainly hepatic.


5.6 Metabolism/Metabolites

In vitro studies demonstrated that venetoclax is predominantly metabolized as a substrate of CYP3A4/5,,.


5.7 Biological Half-Life

The half-life of venetoclax is reported to be 19-26 hours, after administration of a single 50-mg dose,.


5.8 Mechanism of Action

Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are necessary regulators of the apoptotic (anti-cell programmed death) process. This family comprises proapoptotic and prosurvival proteins for various cells. Cancer cells evade apoptosis by inhibiting programmed cell death (apoptosis). The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has demonstrated clinical efficacy in some BCL-2-dependent hematological cancers. Selective inhibition of BCL-2 by venetoclax, sparing BCL-xL enables therapeutic induction of apoptosis without the negative effect of thrombocytopenia,. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins, leading to mitochondrial outer membrane permeabilization and the activation of caspase enzymes. In nonclinical studies, venetoclax has shown cytotoxic activity in tumor cells that overexpress BCL-2.


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About the Company : Egis is an EU-based, vertically integrated generic pharmaceutical company with over 110 years of experience across the entire value chain. Renowned for reliable supply, proprietary...

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About the Company : Alembic Pharmaceuticals Limited is a leading pharmaceutical company in India. The Company is vertically integrated with the ability to develop, manufacture and market pharmaceutica...

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About the Company : Established in 2011 and situated in Hangzhou, Zhejiang, China, Hangzhou Longshine Bio-Tech CO., Ltd is dedicated to providing services for pharmaceutical and chemical products, cat...

Established in 2011 and situated in Hangzhou, Zhejiang, China, Hangzhou Longshine Bio-Tech CO., Ltd is dedicated to providing services for pharmaceutical and chemical products, catering to both export and import markets. The company consists of two primary business departments: the Professional Sourcing/Product Team and the Quality Team. Backed by experienced partners, Longshine has evolved into a trustworthy supplier of high-quality products and received ISO9001:2008 certification in 2017.
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About the Company : We are a world class innovation driven specialty pharmaceutical company with integrated Research, Development, Manufacturing and Marketing of Quality affordable medicines for a Hea...

We are a world class innovation driven specialty pharmaceutical company with integrated Research, Development, Manufacturing and Marketing of Quality affordable medicines for a Healthier Tomorrow. We always strive to focus on area of unmet medical need and leverages our expertise to bring in solutions that improve people’s health better around the world. We are committed to expand the horizons of healthcare by embracing new technologies, touching millions of lives with good health & partnering for a better tomorrow.
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API | Excipient name

Venetoclax

Synonyms

1257044-40-8, Abt-199, Venclexta, Gdc-0199, Abt199, Abt 199

Cas Number

1257044-40-8

Unique Ingredient Identifier (UNII)

N54AIC43PW

About Venetoclax

Venetoclax is an orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia.

Venetoclax Manufacturers

A Venetoclax manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Venetoclax, including repackagers and relabelers. The FDA regulates Venetoclax manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Venetoclax 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 Venetoclax manufacturers with USDMF, JDMF, KDMF, CEP, GMP, and COA related information on PhamaCompass.

Venetoclax Suppliers

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

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

Venetoclax USDMF

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

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

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

Venetoclax KDMF

In Korea, the Ministry of Food and Drug Safety (MFDS) is in charge of regulating pharmaceutical products and services.

Pharmaceutical companies submit a Venetoclax Drug Master File in Korea (Venetoclax KDMF) to the MFDS, which includes comprehensive information about the production, processing, facilities, materials, packaging, and testing of Venetoclax. The MFDS reviews the Venetoclax KDMF as part of the drug registration process and uses the information provided in the Venetoclax KDMF to evaluate the safety and efficacy of the drug.

After submitting a Venetoclax KDMF to the MFDS, the registered manufacturer can provide importers or distributors with the registration number without revealing confidential information to Korean business partners. Applicants seeking to register their Venetoclax API can apply through the Korea Drug Master File (KDMF).

click here to find a list of Venetoclax suppliers with KDMF on PharmaCompass.

Venetoclax WC

A Venetoclax written confirmation (Venetoclax WC) is an official document issued by a regulatory agency to a Venetoclax manufacturer, verifying that the manufacturing facility of a Venetoclax active pharmaceutical ingredient (API) adheres to the Good Manufacturing Practices (GMP) regulations of the importing country. When exporting Venetoclax APIs or Venetoclax finished pharmaceutical products to another nation, regulatory agencies frequently require a Venetoclax WC (written confirmation) as part of the regulatory process.

click here to find a list of Venetoclax suppliers with Written Confirmation (WC) on PharmaCompass.

Venetoclax 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 Venetoclax as an active pharmaceutical ingredient (API).

Finished drug products

The FDA updates the NDC directory daily. The NDC numbers for Venetoclax 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 Venetoclax 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 Venetoclax and are produced by outsourcing facilities. While these outsourcing facilities are not mandated to assign a Venetoclax NDC to their finished compounded human drug products, they may choose to do so.

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

Venetoclax GMP

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

Venetoclax CoA

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

Venetoclax CoA mostly includes findings from lab analyses of a specific batch. For each Venetoclax 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.

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