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Chemistry

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Also known as: Schembl23846781, Ab521, Ex-a9762, Hy-159644, 2709069-30-5
Molecular Formula
C21H17F4NO3S
Molecular Weight
439.4  g/mol
InChI Key
KHBHHNNBNHHGPE-QCCZFBHPSA-N

Casdatifan
Casdatifan is an orally bioavailable allosteric inhibitor of hypoxia inducible factor (HIF)-2alpha, with potential antineoplastic activity. Upon oral administration, casdatifan targets and allosterically binds to a hydrophobic pocket on HIF-2alpha leading to a confirmational change that prevents HIF-2alpha heterodimerization with HIF-1beta and binding to the hypoxia response element (HRE) binding site on DNA. This results in decreased transcription and expression of HIF-2alpha downstream target genes, many of which regulate tumor cell growth and survival. Blocking HIF-2alpha reduces the proliferation of HIF-2alpha-expressing tumor cells. HIF-2alpha, a heterodimeric transcription factor overexpressed under hypoxic conditions in many cancer cell types, promotes proliferation, progression and metastasis of tumors.
1 2D Structure

Casdatifan

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(5R,6S,8R)-3,5,6-trifluoro-8-[(1S,2R)-2-fluoro-1-hydroxy-7-methylsulfonyl-2,3-dihydro-1H-inden-4-yl]-5,6,7,8-tetrahydronaphthalene-1-carbonitrile
2.1.2 InChI
InChI=1S/C21H17F4NO3S/c1-30(28,29)17-3-2-11(13-7-16(24)21(27)19(13)17)12-6-15(23)20(25)14-5-10(22)4-9(8-26)18(12)14/h2-5,12,15-16,20-21,27H,6-7H2,1H3/t12-,15+,16-,20-,21-/m1/s1
2.1.3 InChI Key
KHBHHNNBNHHGPE-QCCZFBHPSA-N
2.2 Synonyms
2.2.1 Depositor-Supplied Synonyms

1. Schembl23846781

2. Ab521

3. Ex-a9762

4. Hy-159644

5. 2709069-30-5

2.3 Create Date
2021-11-10
3 Chemical and Physical Properties
Molecular Weight 439.4 g/mol
Molecular Formula C21H17F4NO3S
XLogP33
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count8
Rotatable Bond Count2
Exact Mass Da
Monoisotopic Mass Da
Topological Polar Surface Area86.5
Heavy Atom Count30
Formal Charge0
Complexity811
Isotope Atom Count0
Defined Atom Stereocenter Count5
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1

Drugs in Development

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Details:

Gilead's window to exercise its option to casdatifan has expired and arcus retains rights to AB521 (casdatifan), a small-molecule inhibitor of HIF-2a.


Lead Product(s): Casdatifan

Therapeutic Area: Oncology Brand Name: AB521

Study Phase: Phase IProduct Type: Other Small Molecule

Sponsor: Gilead Sciences

Deal Size: $1,600.0 million Upfront Cash: $375.0 million

Deal Type: Collaboration February 18, 2025

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01

FCE Pharma
Not Confirmed
FCE Pharma
Not Confirmed

Details : Gilead's window to exercise its option to casdatifan has expired and arcus retains rights to AB521 (casdatifan), a small-molecule inhibitor of HIF-2a.

Product Name : AB521

Product Type : Other Small Molecule

Upfront Cash : $375.0 million

February 18, 2025

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Details:

The net proceeds will support the the clinical development of AB521 (casdatifan), a small-molecule inhibitor of HIF-2a, for the treatment of clear cell renal cell carcinoma.


Lead Product(s): Casdatifan

Therapeutic Area: Oncology Brand Name: AB521

Study Phase: Phase IProduct Type: Other Small Molecule

Sponsor: Goldman Sachs & Co

Deal Size: $150.0 million Upfront Cash: Undisclosed

Deal Type: Public Offering February 18, 2025

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02

FCE Pharma
Not Confirmed
FCE Pharma
Not Confirmed

Details : The net proceeds will support the the clinical development of AB521 (casdatifan), a small-molecule inhibitor of HIF-2a, for the treatment of clear cell renal cell carcinoma.

Product Name : AB521

Product Type : Other Small Molecule

Upfront Cash : Undisclosed

February 18, 2025

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Details:

AB521 (casdatifan) is a small-molecule inhibitor of HIF-2a, which is being evaluated for the treatment of clear cell renal cell carcinoma.


Lead Product(s): Casdatifan,Cabozantinib

Therapeutic Area: Oncology Brand Name: AB521

Study Phase: Phase IProduct Type: Other Small Molecule

Sponsor: Inapplicable

Deal Size: Inapplicable Upfront Cash: Inapplicable

Deal Type: Inapplicable February 15, 2025

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03

FCE Pharma
Not Confirmed
FCE Pharma
Not Confirmed

Details : AB521 (casdatifan) is a small-molecule inhibitor of HIF-2a, which is being evaluated for the treatment of clear cell renal cell carcinoma.

Product Name : AB521

Product Type : Other Small Molecule

Upfront Cash : Inapplicable

February 15, 2025

blank

Details:

AB521 (casdatifan) is a potential best-in-class HIF-2a inhibitor, small molecule drug candidate, which is currently being evaluated for the treatment of renal cell cancer.


Lead Product(s): Casdatifan

Therapeutic Area: Oncology Brand Name: AB521

Study Phase: Phase IProduct Type: Other Small Molecule

Sponsor: Inapplicable

Deal Size: Inapplicable Upfront Cash: Inapplicable

Deal Type: Inapplicable October 24, 2024

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04

FCE Pharma
Not Confirmed
FCE Pharma
Not Confirmed

Details : AB521 (casdatifan) is a potential best-in-class HIF-2a inhibitor, small molecule drug candidate, which is currently being evaluated for the treatment of renal cell cancer.

Product Name : AB521

Product Type : Other Small Molecule

Upfront Cash : Inapplicable

October 24, 2024

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Details:

The proceeds will be used to rapidly advance AB521 (casdatifan), its potential best-in-class HIF-2a inhibitor, for the treatment of renal cell cancer.


Lead Product(s): Casdatifan,Encoberminogene Rezmadenovec

Therapeutic Area: Oncology Brand Name: AB521

Study Phase: Phase I/ Phase IIProduct Type: Other Small Molecule

Sponsor: Hercules Capital

Deal Size: Undisclosed Upfront Cash: Undisclosed

Deal Type: Financing August 27, 2024

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05

FCE Pharma
Not Confirmed
FCE Pharma
Not Confirmed

Details : The proceeds will be used to rapidly advance AB521 (casdatifan), its potential best-in-class HIF-2a inhibitor, for the treatment of renal cell cancer.

Product Name : AB521

Product Type : Other Small Molecule

Upfront Cash : Undisclosed

August 27, 2024

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Details:

The collaboration aims to evaluate AB521 (casdatifan), an investigational HIF-2a inhibitor, in combination with volrustomig, AstraZeneca’s PD-1/CTLA-4 bispecific antibody, in patients with ccRCC.


Lead Product(s): Casdatifan,Volrustomig

Therapeutic Area: Oncology Brand Name: AB521

Study Phase: PreclinicalProduct Type: Other Small Molecule

Sponsor: AstraZeneca

Deal Size: Undisclosed Upfront Cash: Undisclosed

Deal Type: Collaboration February 10, 2024

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06

FCE Pharma
Not Confirmed
FCE Pharma
Not Confirmed

Details : The collaboration aims to evaluate AB521 (casdatifan), an investigational HIF-2a inhibitor, in combination with volrustomig, AstraZeneca’s PD-1/CTLA-4 bispecific antibody, in patients with ccRCC.

Product Name : AB521

Product Type : Other Small Molecule

Upfront Cash : Undisclosed

February 10, 2024

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Details:

The companies will enter into a clinical trial collaboration evaluating XL092 (zanzalintinib), a tyrosine kinase inhibitor, in combination with AB521 in patients with advanced solid tumors including clear cell renal cell carcinoma.


Lead Product(s): Encoberminogene Rezmadenovec,Casdatifan

Therapeutic Area: Oncology Brand Name: XL092

Study Phase: IND EnablingProduct Type: Cell and Gene therapy

Sponsor: Arcus Biosciences

Deal Size: Undisclosed Upfront Cash: Undisclosed

Deal Type: Collaboration April 12, 2023

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07

Exelixis

U.S.A
arrow
FCE Pharma
Not Confirmed

Exelixis

U.S.A
arrow
FCE Pharma
Not Confirmed

Details : The companies will enter into a clinical trial collaboration evaluating XL092 (zanzalintinib), a tyrosine kinase inhibitor, in combination with AB521 in patients with advanced solid tumors including clear cell renal cell carcinoma.

Product Name : XL092

Product Type : Cell and Gene therapy

Upfront Cash : Undisclosed

April 12, 2023

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Details:

Initial pharmacokinetic /pharmacodynamic data for AB521, a Clinical-Stage, Potent, and Selective Hypoxia-Inducible Factor (HIF)-2α Inhibitor, in healthy volunteers, confirm its potential to have an improved clinical profile compared to that of only approved HIF-2a inhibitor.


Lead Product(s): Casdatifan

Therapeutic Area: Oncology Brand Name: AB521

Study Phase: Phase IProduct Type: Other Small Molecule

Sponsor: Inapplicable

Deal Size: Inapplicable Upfront Cash: Inapplicable

Deal Type: Inapplicable August 03, 2022

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08

FCE Pharma
Not Confirmed
FCE Pharma
Not Confirmed

Details : Initial pharmacokinetic /pharmacodynamic data for AB521, a Clinical-Stage, Potent, and Selective Hypoxia-Inducible Factor (HIF)-2α Inhibitor, in healthy volunteers, confirm its potential to have an improved clinical profile compared to that of only appr...

Product Name : AB521

Product Type : Other Small Molecule

Upfront Cash : Inapplicable

August 03, 2022

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Details:

Preclinical research related to therapeutic opportunities to enhance anti-tumor immunity and new insights into the benet of dual A2a/A2b adenosine receptor antagonism, CD39 inhibition and HPK1 inhibition will be presented at the American Association for Cancer Research.


Lead Product(s): Casdatifan

Therapeutic Area: Oncology Brand Name: AB521

Study Phase: Phase IProduct Type: Other Small Molecule

Sponsor: Inapplicable

Deal Size: Inapplicable Upfront Cash: Inapplicable

Deal Type: Inapplicable August 03, 2022

blank

09

FCE Pharma
Not Confirmed
FCE Pharma
Not Confirmed

Details : Preclinical research related to therapeutic opportunities to enhance anti-tumor immunity and new insights into the benet of dual A2a/A2b adenosine receptor antagonism, CD39 inhibition and HPK1 inhibition will be presented at the American Association for ...

Product Name : AB521

Product Type : Other Small Molecule

Upfront Cash : Inapplicable

August 03, 2022

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