SSTR3/5
BIM-23056 targets somatostatin receptors sst3 and sst5 as a potent antagonist with Ki values of 10.8 nM and 5.7 nM, respectively. It also binds to sst1 (Ki = 142 nM), sst4 (Ki = 16.6 nM), and sst2 (Ki >1000 nM). The compound acts as an antagonist on SRIF14-induced [35S]-GTPγS binding at sst3 and sst5 receptors. Its selectivity for sst3 and sst5 makes it a valuable tool for studying the specific roles of these somatostatin receptor subtypes in various physiological and pathological processes.

For sst1, sst4, and sst2, BIM 23056 has Ki values of 142, 16.6, and >1000, respectively[1].

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In vitro studies demonstrate that BIM-23056 is a potent sst3 and sst5 somatostatin receptor antagonist with Ki values of 10.8 nM and 5.7 nM, respectively. It has Ki values of 142 nM for sst1, 16.6 nM for sst4, and >1000 nM for sst2. The compound acts as an antagonist on SRIF14-induced [35S]-GTPγS binding at sst3 and sst5 receptors with pKB values of 6.33 and 5.84, respectively. Its selectivity profile makes it a valuable research tool for studying the specific roles of sst3 and sst5 receptors in somatostatin-mediated signaling.

In vivo studies of BIM-23056 are limited in publicly available literature. As a potent sst3 and sst5 antagonist, the compound can be used to study the physiological and pathological roles of these somatostatin receptor subtypes in vivo. Somatostatin receptors are involved in various physiological processes including hormone secretion, neurotransmission, and cell proliferation. The compound's selectivity for sst3 and sst5 makes it useful for elucidating subtype-specific functions in animal models. However, specific in vivo efficacy data and detailed animal model studies are not extensively reported. Further research is needed to establish its in vivo activity profile.

1. Somatostatin (SRIF) causes a concentration-dependent inhibition of neurotransmission in guinea-pig ileum and vas deferens as well as negative inotropy in guinea-pig isolated right atrium. The SRIF receptors mediating these effects have now been further characterized by use of the peptides BIM-23027, BIM-23056  and L-362855, reported as selective for the recombinant SRIF receptor types, sst2, sst3 and sst5, respectively. 2. BIM-23027 was a highly potent agonist at causing an inhibition of neurotransmission in the guinea-pig ileum (EC50 value 1.9 nM), being about 3 times more potent than SRIF (EC50 value 6.8 nM). In contrast, in both guinea-pig vas deferens and right atrial preparations, BIM-23027 was a relatively weak agonist being at least 30-100 times weaker than SRIF. In guinea-pig atria, BIM-23027 (3 microM) antagonized the negative inotropic action of SRIF28 (apparent pKB = 5.9 +/- 0.1) but had no effect on the negative inotropic action of cyclohexyladenosine. 3. The inhibitory effect of BIM-23027 in the guinea-pig ileum was readily desensitized. Prior exposure to BIM-23027 (0.3 microM) markedly attenuated the inhibitory effect of SRIF but had no effect on the inhibitory action of clonidine suggesting that BIM-23027 and SRIF act via a common receptor mechanism. 4. L-362855 caused a concentration-dependent inhibition of neurotransmission in both the guinea-pig ileum and vas deferens as well as causing negative inotropy in the guinea-pig atrium but was at least 30-100 times weaker than SRIF. In guinea-pig isolated atria, L-362855 (3 microM) did not antagonize the negative inotropic action of SRIF28. 5. BIM-23056  in concentrations up to 1 microM was inactive as an agonist in guinea-pig isolated ileum, vas deferens and atrium and did not antagonize the inhibitory actions of SRIF in any of these preparations.6. The results from this study support our previous contention that the sst2 receptor type mediates inhibition of neurotransmission by SRIF in the guinea-pig ileum. The SRIF receptor type mediating inhibition of neurotransmission in the guinea-pig vas deferens appears different, but similar, to that mediating negative inotropy in the atrium. However the characteristics of these latter receptors appear different from that of the recombinant sst2, sst3 and sst5 receptors for SRIF described for rat and man.[2]

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For somatostatin receptor binding assays, membrane preparations from cells expressing human recombinant sst1-sst5 receptors are incubated with radiolabeled somatostatin analogs (e.g., [125I]-Tyr11-somatostatin) and varying concentrations of BIM-23056. Non-specific binding is determined using excess unlabeled somatostatin. Following incubation at appropriate temperature (typically 25°C for 60-120 minutes), bound and free radioligands are separated by rapid filtration through glass fiber filters. Filters are washed and radioactivity counted. Ki values are calculated from competition curves using the Cheng-Prusoff equation. For functional assays, [35S]-GTPγS binding is measured to assess receptor activation. Assays are performed in triplicate with appropriate controls.

For in vitro cellular assays, cells expressing somatostatin receptors (e.g., CHO or HEK293 cells transfected with sst1-sst5) are cultured in appropriate media under standard conditions (37°C, 5% CO2). BIM-23056 is dissolved in DMSO or appropriate buffer and diluted in culture medium to desired concentrations. Cells are treated with compound and somatostatin-induced signaling (e.g., cAMP inhibition, calcium mobilization) is measured. For [35S]-GTPγS binding assays, membrane preparations are incubated with GDP, [35S]-GTPγS, and SRIF14 with or without compound. Each concentration is tested in replicate wells with vehicle controls and positive controls.

For in vivo animal studies of BIM-23056, no specific published protocols are available. For general in vivo administration of somatostatin receptor antagonists, compounds are typically formulated in suitable vehicles and administered via intraperitoneal (i.p.) injection, intravenous (i.v.) injection, or subcutaneous (s.c.) injection. Dosing regimens vary by study objective. For endocrine studies, hormone levels may be measured after compound administration. All procedures must follow institutional animal care and use committee guidelines.

Pharmacokinetic properties of BIM-23056 are characteristic of a linear octapeptide. The compound has a molecular weight of 1060.25, formula C48H65N13O12S2, and CAS number 150155-61-6. Purity: ≥95% (HPLC). Storage: typically at -20°C for powder; in solvent at -80°C. As a peptide, it is typically administered parenterally and may have limited oral bioavailability. Specific pharmacokinetic parameters such as half-life, clearance, and bioavailability are not extensively reported in publicly available sources.

According to available safety information, BIM-23056 is intended for research purposes only. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. No clinical toxicity data are available.

[1]. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1-5). Endocrinology. 1994 Dec;135(6):2814-7.

[2]. Further evidence from functional studies for somatostatin receptor heterogeneity in guinea-pig isolated ileum, vas deferens and right atrium. Br J Pharmacol. 1995 Jul;115(6):975-80.

This study investigated five different receptor ligands: BIM-23027 (SST2 receptor agonist; Bell & Reisine, 1993), CYN-154806 (SST2 receptor antagonist; Bass et al., 1996), NNC 26-9100 (SST4 receptor agonist; Ankersen et al., 1998), L-362,855 (SST2,5 receptor agonist; Williams et al., 1997), and BIM-23056 (SST5 receptor antagonist; Wilkinson et al., 1997). All ligands were administered via a microdialysis probe (reverse dialysis). A 90-minute dialysate sample was collected to establish a baseline. All compounds were dissolved in Klinefelter-Ringer's solution (containing neostigmine), and reverse dialysis was performed for 15 minutes at 90 and 135 minutes after sampling. Between dialysis sessions, the perfusion fluid was changed to Kjeldahl-Ringer solution. In experiments using NNC 26-9100, L-362,855, and BIM-23056, each compound was tested at three concentrations (1, 50, and 1000 nm). Br J Pharmacol. 1999 Nov; 128(6): 1346–1352.

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BIM-23056 is a linear octapeptide and a potent sst3 and sst5 somatostatin receptor antagonist with Ki values of 10.8 nM and 5.7 nM, respectively. It also binds to sst1 (Ki = 142 nM), sst4 (Ki = 16.6 nM), and sst2 (Ki >1000 nM). It acts as an antagonist on SRIF14-induced [35S]-GTPγS binding at sst3 and sst5. It has a molecular weight of 1060.25 and formula C48H65N13O12S2. It is for research use only with no clinical development or regulatory approvals reported.

C71H81N11O9

1232.47

1231.62

150155-61-6

BIM-23056 TFA;1426173-61-6

16133799

White to off-white solid powder

9.611

12

11

32

91

2320

8

CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](CC2=CC3=CC=CC=C3C=C2)C(=O)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC4=CNC5=CC=CC=C54)NC(=O)[C@H](CC6=CC=C(C=C6)O)NC(=O)[C@H](CC7=CC=CC=C7)NC(=O)[C@@H](CC8=CC=CC=C8)N

VPTPBEUWKCLZGU-OOSWLFMASA-N

InChI=1S/C71H81N11O9/c1-44(2)63(71(91)81-61(39-47-22-10-5-11-23-47)67(87)77-58(64(74)84)41-49-29-32-50-24-12-13-25-51(50)36-49)82-66(86)57(28-16-17-35-72)76-70(90)62(42-52-43-75-56-27-15-14-26-54(52)56)80-69(89)60(40-48-30-33-53(83)34-31-48)79-68(88)59(38-46-20-8-4-9-21-46)78-65(85)55(73)37-45-18-6-3-7-19-45/h3-15,18-27,29-34,36,43-44,55,57-63,75,83H,16-17,28,35,37-42,72-73H2,1-2H3,(H2,74,84)(H,76,90)(H,77,87)(H,78,85)(H,79,88)(H,80,89)(H,81,91)(H,82,86)/t55-,57+,58-,59+,60+,61+,62-,63+/m1/s1

(2S)-6-amino-N-[(2S)-1-[[(2S)-1-[[(2R)-1-amino-3-naphthalen-2-yl-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanamide

BIM 23056; D-Alaninamide, D-phenylalanyl-L-phenylalanyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-phenylalanyl-3-(2-naphthalenyl)-; (2S)-6-Amino-N-[(2S)-1-[[(2S)-1-[[(2R)-1-amino-3-naphthalen-2-yl-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanamide; FFYWKVFA; D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2; CHEMBL410596; SCHEMBL12912367;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 100 mg/mL (81.14 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (2.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)