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BIRT 377 

Cat. No. M29280
BIRT 377  Structure
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Biological Activity

BIRT 377 is a potent amd orally bioavailable inhibitor of the interaction between intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1), with a Ki of 25.8 nM. BIRT 377 also inhibits the production of IL-2 in vivo. BIRT 377 can be used for researching inflammatory and immune disorders.

Chemical Information
Molecular Weight 442.13
Formula C18H15BrCl2N2O2
CAS Number 213211-10-0
Form Solid
Solubility (25°C) DMSO 100 mg/mL (ultrasonic)
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Aaron Johnson, et al. Org Biomol Chem. Stereodivergent synthesis of the LFA-1 antagonist BIRT-377 by porcine liver esterase desymmetrization and Curtius rearrangement

[2] Naidu S Chowdari, et al. Org Lett. Total synthesis of LFA-1 antagonist BIRT-377 via organocatalytic asymmetric construction of a quaternary stereocenter

[3] K M Wasan, et al. Pharm Res. Rat and rabbit plasma distribution of free and chylomicron-associated BIRT 377, a novel small molecule antagonist of LFA-1-mediated cell adhesion

[4] S R Kapadia, et al. J Org Chem. An improved synthesis of chiral alpha-(4-bromobenzyl)alanine ethyl ester and its application to the synthesis of LFA-1 antagonist BIRT-377

[5] N K Yee. Org Lett. Self-regeneration of stereocenters: a practical enantiospecific synthesis of LFA-1 antagonist BIRT-377

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