Target Validation Information
TTD ID	T11011
Target Name	Corticotropin-releasing factor receptor 2 (CRHR2)
Type of Target	Clinical trial
Drug Potency against Target	Urocortin 2	Drug Info	IC50 = 0.1 nM	[2]
Action against Disease Model	Urocortin 2	Drug Info	K41498 showed high affinity binding to hCRF(2alpha) (K(i)=0.66+/-0.03 nM) and hCRF(2beta) (K(i)=0.62+/-0.01 nM) but not the hCRF(1) receptor (k(i)=425+50 nM) and decreased Svg-stimulated cAMP acc uMulation in hCRF(2) expressing cells. In conscious Wistar-Kyoto rats, K41498 (1.84 microg, i.v.) antagonized the hypotensive response to systemic urocortin (1.4 microg, i.v.), but did not block the pressor response to centrally administered urocortin (2.35 microg, i.c.v.). 3. K41498 was subsequently radio-iodinated, and in autoradiographic studies, specific (sensitive to rat urocortin, astressin and aSvg30, but insensitive to antalarmin) binding of (125)I-K41498 (100 pM) was detected in the heart and in selected brain regions including the nucleus tractus solitarius (NTS), spinal trigeminal nucleus, lateral sept uM and around the anterior and middle cerebral arteries. 4. Following unilateral nodose ganglionectomy, binding of (125)I-K41498 was reduced by 65% in the ipsilateral NTS, indicative of presynaptic CRF(2) receptors on vagal afferent terminals	[1]
References
REF 1	The highly selective CRF(2) receptor antagonist K41498 binds to presynaptic CRF(2) receptors in rat brain. Br J Pharmacol. 2002 Jul;136(6):896-904.
REF 2	Small molecule inhibitors of phosphoinositide 3-kinase (PI3K) delta and gamma. Curr Top Med Chem. 2009;9(8):738-53.

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