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Chemistry

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Also known as: Abl-001, 1492952-76-7, Abl001, Asciminib free base, Abl001-nx, Nvp-abl001
Molecular Formula
C20H18ClF2N5O3
Molecular Weight
449.8  g/mol
InChI Key
VOVZXURTCKPRDQ-CQSZACIVSA-N
FDA UNII
L1F3R18W77

Asciminib
Asciminib is an orally bioavailable, allosteric Bcr-Abl1 tyrosine kinase inhibitor, with antineoplastic activity. Upon administration, asciminib targets and binds to the myristoyl pocket of the Bcr-Abl1 fusion protein at a location that is distinct from the ATP-binding domain, thereby inhibiting the activity of both wild-type Bcr-Abl and certain mutation forms, including the T315I mutation. This binding results in the inhibition of Bcr-Abl1-mediated proliferation and enhanced apoptosis of Philadelphia chromosome-positive (Ph+) hematological malignancies. The Bcr-Abl1 fusion protein tyrosine kinase is an abnormal enzyme produced by leukemia cells that contain the Philadelphia chromosome.
1 2D Structure

Asciminib

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
N-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide
2.1.2 InChI
InChI=1S/C20H18ClF2N5O3/c21-20(22,23)31-15-3-1-13(2-4-15)26-19(30)12-9-16(17-5-7-25-27-17)18(24-10-12)28-8-6-14(29)11-28/h1-5,7,9-10,14,29H,6,8,11H2,(H,25,27)(H,26,30)/t14-/m1/s1
2.1.3 InChI Key
VOVZXURTCKPRDQ-CQSZACIVSA-N
2.1.4 Canonical SMILES
C1CN(CC1O)C2=C(C=C(C=N2)C(=O)NC3=CC=C(C=C3)OC(F)(F)Cl)C4=CC=NN4
2.1.5 Isomeric SMILES
C1CN(C[C@@H]1O)C2=C(C=C(C=N2)C(=O)NC3=CC=C(C=C3)OC(F)(F)Cl)C4=CC=NN4
2.2 Other Identifiers
2.2.1 UNII
L1F3R18W77
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Abl001

2. Asciminib Hydrochloride

2.3.2 Depositor-Supplied Synonyms

1. Abl-001

2. 1492952-76-7

3. Abl001

4. Asciminib Free Base

5. Abl001-nx

6. Nvp-abl001

7. Asciminib [usan]

8. Scemblix

9. Example 9

10. L1f3r18w77

11. 1492952-76-7 (free Base)

12. (r)-n-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1h-pyrazol-5-yl)nicotinamide

13. 3-pyridinecarboxamide, N-(4-(chlorodifluoromethoxy)phenyl)-6-((3r)-3-hydroxy-1-pyrrolidinyl)-5-(1h-pyrazol-3-yl)-

14. N-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3r)-3-hydroxypyrrolidin-1-yl]-5-(1h-pyrazol-5-yl)pyridine-3-carboxamide

15. 3-pyridinecarboxamide, N-[4-(chlorodifluoromethoxy)phenyl]-6-[(3r)-3-hydroxy-1-pyrrolidinyl]-5-(1h-pyrazol-3-yl)-

16. Asciminib [inn]

17. Asciminib (abl001)

18. Asciminib (usan/inn)

19. Asciminib [who-dd]

20. Unii-l1f3r18w77

21. Gtpl8962

22. Chembl4208229

23. Schembl15388306

24. Tqp0925

25. Ex-a3030

26. Bdbm50459091

27. Nsc789925

28. S8555

29. Zinc150275965

30. At30330

31. Ccg-269232

32. Compound 1 [pmid: 30137981]

33. Cs-7655

34. Db12597

35. Nsc-789925

36. (r)-n- (4-(chlorodifluoromethoxy)phenyl)- 6-(3- Hydroxypyrrolidin-1- Yl)-5- (1h-pyrazol- 5-yl)nicotinamide

37. Ba166957

38. Bs-15538

39. Hy-104010

40. D11403

41. A910986

42. Q27074535

43. (r)-n-(4-(chloro Difluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1h-pyrazol-5-yl)nicotinamide

44. (r)-n-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1h-pyrazol-3-yl)nicotinamide

45. Ay7

46. N-(4-(chlorodifluoromethoxy)phenyl)-6-((3r)-3- Hydroxypyrrolidin-1-yl)-5-(1h-pyrazol-3-yl)pyridine- 3-carboxamide

2.4 Create Date
2013-12-02
3 Chemical and Physical Properties
Molecular Weight 449.8 g/mol
Molecular Formula C20H18ClF2N5O3
XLogP33
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count8
Rotatable Bond Count6
Exact Mass449.1066235 g/mol
Monoisotopic Mass449.1066235 g/mol
Topological Polar Surface Area103 Ų
Heavy Atom Count31
Formal Charge0
Complexity626
Isotope Atom Count0
Defined Atom Stereocenter Count1
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

Asciminib is indicated for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase who have been previously treated with 2 tyrosine kinase inhibitors. It is also indicated in the treatment of Ph+ CML in adult patients with the T315I mutation.


Scemblix is indicated for the treatment of adult patients with Philadelphia chromosome positive chronic myeloid leukaemia in chronic phase (Ph+ CML CP) previously treated with two or more tyrosine kinase inhibitors (see section 5. 1).


5 Pharmacology and Biochemistry
5.1 Pharmacology

Asciminib exerts its therapeutic activity by inhibiting an oncogenic protein responsible for the proliferation of CML. It may be administered orally once or twice a day depending on the condition being treated. By increasing the total daily dose 5-fold as compared to standard therapy (80mg daily vs. 400mg daily), it can be used to treat Ph+ CML with the T315I mutation, a typically treatment-resistant variant of the disease. As with many other chemotherapeutic agents, asciminib treatment can result in various forms of myelosuppression, including thrombocytopenia and neutropenia. Patients should receive frequent laboratory monitoring throughout therapy and dose adjustments may be required based on the severity of observed effects. Patients may also experience pancreatic and/or cardiovascular toxicity, both of which require frequent monitoring and may require dose adjustments as per prescribing information.


5.2 ATC Code

L01EA06


L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01E - Protein kinase inhibitors

L01EA - Bcr-abl tyrosine kinase inhibitors

L01EA06 - Asciminib


5.3 Absorption, Distribution and Excretion

Absorption

The median Tmax of asciminib following oral administration is 2.5 hours. At a dose of 80mg once daily, the steady-state Cmax and AUCtau were 1781 ng/mL and 15112 ng.h/mL, respectively. At a dose of 40mg twice daily, the steady-state Cmax and AUCtau were 793 ng/mL and 5262 ng.h/mL, respectively. At a dose of 200mg twice daily (for treatment of T315I mutants), the steady-state Cmax and AUCtau were 5642 ng/mL and 37547 ng.h/mL, respectively. As compared to the fasted state, the co-administration of asciminib with a high-fat meal decreased the AUC and Cmax by 62% and 68%, respectively, and its co-administration with a low-fat meal decreased the AUC and Cmax by 30% and 35%, respectively.


Route of Elimination

Asciminib is eliminated via biliary secretion facilitated by breast cancer-resistant protein (BCRP) transporters. Following oral administration, approximately 80% and 11% of an asciminib dose was recovered in the feces and urine, respectively. Unchanged parent drug accounted for 57% of drug material recovered in the feces and 2.5% in the urine.


Volume of Distribution

At steady-state, the apparent volume of distribution of asciminib is 151 L.


Clearance

The total apparent clearance of asciminib is 6.7 L/h at a total daily dose of 80mg and 4.1 L/h at a dose of 200mg twice daily.


5.4 Metabolism/Metabolites

Asciminib is negligibly metabolized, with unchanged parent drug comprising the main drug component in plasma (~93%) and following excretion (~57% in feces). The main circulating metabolites are M30.5, M44, and M29.5, accounting for approximately 5%, 2%, and 0.4% of the total administered dose, respectively. The oxidative metabolism of asciminib is mediated by CYP3A4, and the glucuronidation of asciminib is mediated by UGT2B7 and UGT2B17.


5.5 Biological Half-Life

The terminal elimination half-life asciminib is 5.5 hours when administered at 40mg twice daily and 9.0 hours when administered at 200mg twice daily.


5.6 Mechanism of Action

In most patients with chronic myeloid leukemia (CML), progression of the disease is driven primarily by a translocation of the Philadelphia chromosome that creates an oncogenic fusion gene, _BCR-ABL1_, between the _BCR_ and _ABL1_ genes. This fusion gene produces a resultant fusion protein, BCR-ABL1, which exhibits elevated tyrosine kinase and transforming activities that contribute to CML proliferation. Asciminib is an allosteric inhibitor of the BCR-ABL1 tyrosine kinase. It binds to the myristoyl pocket of the ABL1 portion of the fusion protein and locks it into an inactive conformation, preventing its oncogenic activity.


API Reference Price

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21-Dec-2023
21-Dec-2023
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ABOUT THIS PAGE

Looking for 1492952-76-7 / Asciminib API manufacturers, exporters & distributors?

Asciminib manufacturers, exporters & distributors 1

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PharmaCompass offers a list of Asciminib 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 Asciminib manufacturer or Asciminib supplier for your needs.

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

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

API | Excipient name

Asciminib

Synonyms

Abl-001, 1492952-76-7, Abl001, Asciminib free base, Abl001-nx, Nvp-abl001

Cas Number

1492952-76-7

Unique Ingredient Identifier (UNII)

L1F3R18W77

About Asciminib

Asciminib is an orally bioavailable, allosteric Bcr-Abl1 tyrosine kinase inhibitor, with antineoplastic activity. Upon administration, asciminib targets and binds to the myristoyl pocket of the Bcr-Abl1 fusion protein at a location that is distinct from the ATP-binding domain, thereby inhibiting the activity of both wild-type Bcr-Abl and certain mutation forms, including the T315I mutation. This binding results in the inhibition of Bcr-Abl1-mediated proliferation and enhanced apoptosis of Philadelphia chromosome-positive (Ph+) hematological malignancies. The Bcr-Abl1 fusion protein tyrosine kinase is an abnormal enzyme produced by leukemia cells that contain the Philadelphia chromosome.

Asciminib Manufacturers

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

Asciminib Suppliers

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

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

Asciminib 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 Asciminib as an active pharmaceutical ingredient (API).

Finished drug products

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

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

Asciminib GMP

Asciminib 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 Asciminib 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 Asciminib GMP manufacturer or Asciminib GMP API supplier for your needs.

Asciminib CoA

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

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

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