PRN1008 free base · Synonyms: Rilzabrutinib

PRN1008 is a reversible covalent, selective and oral active inhibitor of Bruton's Tyrosine Kinase.

For research use only. Not for human or veterinary use.

Target Btk

Research area Metabolic Disease Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

PRN1008 structure

CAS No.: 1575596-29-0

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
100 mg	USD 498.00	BP-01901-100mg	In stock	Get quote
250 mg	USD 920.00	BP-01901-250mg	In stock	Get quote
500 mg	USD 1,420.00	BP-01901-500mg	In stock	Get quote
1 g	USD 2,380.00	BP-01901-1g	In stock	Get quote
5 g	Inquire	BP-01901-5g	Inquire	Inquire
10 g	Inquire	BP-01901-10g	Inquire	Inquire

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Description

PRN1008 is a reversible covalent, selective and oral active inhibitor of Bruton's Tyrosine Kinase (BTK), with an IC50 of 1.3 nM.

Biological activity

In Vitro Rilzabrutinib is a reversible covalent inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC50 of 1.3±0.5 nM. Rilzabrutinib is also found to be highly selectively when tested in a panel of 251 other kinases. Cysteine targeting of BTK by Rilzabrutinib results in a slow off-rate demonstrated by retention of 79±2% of binding to BTK in PBMC 18 hours after washing away the compound in vitro. The covalent cysteine binding is completely reversible after denaturation of the target. Anti-IgM induces human B cell proliferation (10% serum) and B cell CD69 expression are inhibited by Rilzabrutinib with IC50 of 5±2.4 nM and 123±38 nM, respectively. In Vivo In vivo Rilzabrutinib demonstrates enduring pharmacodynamic effects after the compound has cleared from circulation, consistent with extended target residence time. Rilzabrutinib also reverses and completely suppresses collagen-induced arthritis in rats in a dose dependent manner which allows correlation of target occupancy and disease modification.

Identifiers

SMILES: NC1=C2C(C3=C(C=C(OC4=CC=CC=C4)C=C3)F)=NN([C@H]5CN(CCC5)C(/C(C#N)=C/C(C)(N6CCN(C7COC7)CC6)C)=O)C2=NC=N1
InChIKey: LCFFREMLXLZNHE-GBOLQPHISA-N

Specifications

MW (average): 665.7597
Formula: C₃₆H₄₀FN₉O₃
CAS No.: 1575596-29-0
Physical state: Solid
Color: White to off-white
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

References

[1]. Smith PF, et al. A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton's tyrosine kinase, in healthy volunteers. Br J Clin Pharmacol. 2017 Nov;83(11):2367-2376.

[2]. Hill RJ, Bradshaw JM, Bisconte A, Tam D, Owens TD, Brameld KA, Smith PF, Funk JO, Goldstein DM, Nunn PA. Preclinical Characterization of PRN1008, a Novel Reversible Covalent Inhibitor of BTK that Shows Efficacy in a RAT Model of Collagen-Induced Arthritis. Annals of the Rheumatic Diseases 2015; 74(Suppl 2): 216.

Same target

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Same research area

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