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CNTX-0290 is a small molecule somatostatin receptor type 4 (SSTR4) agonist currently in Phase I testing as a potential non-opioid treatment for chronic pain conditions.
CNTX-0290, is a novel, small molecule somatostatin receptor type 4 (SSTR4) agonist that is currently being studied in Phase 1 clinical testing as a potential non-opioid treatment for chronic pain conditions.
CC1 pretreatment was performed using the OptiView method for 8-72 min (except for SSTR3 with protease pretreatment for 4 min), followed by incubation with primary antibodies (SSTR1: 1:3000 (Gramsch, Schwabhausen, Germany), SSTR2A: 1: 500 (Dianova, Hamburg, Germany), SSTR3: 1: 250 (Abcam, Cambridge, United Kingdom), SSTR4: 1: 1000 (Gentex, Zeeland, United States), SSTR5: 1:100 (Abcam, Cambridge, United Kingdom), alpha-subunit: 1: 400 (Immunotech, Prague, Czech Republic), PIT-1: 1:200 (8 min) (Cell Signaling Technology, Danvers, United States)) at 37[degrees]C for 32 min if not stated otherwise.
SSTR4. A total of 235 adenoma samples were stained for SSTR4 expression.
Recurrent CD cases showed a significantly higher expression of SSTR1 (p = 0.0351) and SSTR4 (p = 0.0174) while SSTR5 ID scores were lower than in primary corticotroph adenomas (p = 0.0370).
In 1994, Greenman and Melmed analyzed SSTR 3, SSTR4, and SSTR5 in 33 pituitary adenomas and SSTR1 and SSTR2 in 27 pituitary adenomas using RT-PCR, including 2 and 3 ACTH-producing adenomas, respectively.
In CD, recurrent tumors had significantly higher expression rates of SSTR1 and SSTR4 and significantly lower expression of SSTR5.
Recurrent corticotroph pituitary adenomas show a different SSTR expression with lower SSTR5 levels and higher expression of SSTR1 and SSTR4. We proclaim the need to assess the expression of SSTR1-5 on a routine basis in corticotroph pituitary adenomas to allow individual treatment decisions and to gain experience about receptor dynamics during treatment.
Caption: Figure 3: Expression of SSTR1 (a), SSTR2A (b), SSTR3 (c), SSTR4 (d), and SSTR5 (e) in pituitary adenomas.
Interestingly, somatostatin exhibits the neuronal inflammatory-inhibitory effects via SSTR4 receptor .
CNTX-0290, a first-in-class, potent and selective somatostatin SSTR4 agonist, is a completely novel pain target.
The authors concluded by suggesting further studies with different SST-analogues with a higher affinity for SSTR1 and SSTR4 (expressed by prostate cancer), not adequately addressed with DOTATOC.
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