2-pam

Pralidoxime Chloride (2-PAM chloride) is a useful agent in the treatment of organophosphate poisoning. Pralidoxime binds to organophosphate-inactivated acetylcholinesterase, used to combat poisoning by organophosphates or acetylcholinesterase inhibitors (nerve agents).

Pralidoxime Iodide is an effective AChE reactivator and antidote for organophosphorus poisoning, reactivating AChE inhibited by nerve agents through nucleophilic attack on the phosphorus centre of the neurotoxin.

Darigabat (PF-06372865) is an orally active and selective GABAA receptor modulator that crosses the blood-brain barrier and exhibits anxiolytic activity, with Ki values of 2.9 nM, 21 nM, and 134 nM for α2, α1 PAM, and α2 PAM, respectively.Darigabat is used in the study of anxiety disorders and epilepsy.

JNJ-42153605 is a mGlu2 receptor positive allosteric modulator (EC50: 17 nM).

HM5023507, an orally active dual inhibitor of δγ isoforms in immune signaling. HM5023507 inhibited PI3Kδ and PI3Kγ isoforms with greater than 100-fold selectivity against PI3Kα and PI3Kβ in recombinant enzymatic assays and in primary human immune cells with an exquisite selectivity against other targets.

COR659 is a GABAB positive allosteric modulator (PAM) . COR659 suppresses alcohol and chocolate self-administration in rats[1]. COR659 apparently exerts its effects via a composite mechanism, including positive allosteric modulation of the GABAB receptor and an action at the cannabinoid CB1 receptor[3]. COR659 (0, 2.5, 5 and 10 mg/kg) treatment is completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats[1].COR659 is able to suppress lever-responding for a sucrose solution in sP rats and a chocolate solution in Wistar rats[2]. Animal Model: Male sP and Wistar rats[1]. [1]. Paola Maccioni, et al. Suppressing effect of COR659 on alcohol, sucrose, and chocolate self-administration in rats: involvement of the GABA B and cannabinoid CB 1 receptors. Psychopharmacology (Berl). 2017 Sep;234(17):2525-2543. [2]. Francesca Ferlenghi, et al. The GABA B receptor positive allosteric modulator COR659: In vitro metabolism, in vivo pharmacokinetics in rats, synthesis and pharmacological characterization of metabolically protected derivatives. Eur J Pharm Sci. 2020 Dec 1;155:105544. [3]. Paola Maccioni, et al. Anti-addictive properties of COR659 - Additional pharmacological evidence and comparison with a series of novel analogues. Alcohol. 2019 Mar;75:55-66.

JNJ-46281222 is a metabotropic glutamate (mGlu) 2-selective, highly potent positive allosteric modulator (PAM) with nanomolar affinity (Kd = 1.7 nM) and high modulatory potency (pEC50 = 7.71).

NS11394 is a effective and subtype-selective GABA(A) receptor-positive modulator; possesses a functional efficacy selectivity profile of α(5) > α(3) > α(2) > α(1) at GABA(A) alpha subunit-containing receptors.

MRS7935 (compound 15) is a positive allosteric modulator (PAM) of the A1 adenosine receptor (A1AR), with an EC50 of approximately 2 μM.

α7nAChRModulator-2 (Compound 7b) is an α7nAChR positive allosteric modulator (PAM) with an EC50 of 2.1 μM. It is utilized in research focused on cognitive impairment.

M4mAChRModulator-2 is an orally active and selective positive allosteric modulator (PAM) of the M4 muscarinic acetylcholine receptor (M4mAChR) capable of crossing the blood-brain barrier, with an EC50 of 513 nM. It demonstrates high target selectivity, showing minimal affinity and low inhibition rates for non-target receptors (D1R/D2R/D3R, 5-HT subtypes, κ/δ/μ opioid receptors, H1, M1/M2), while specifically binding to M4mAChR with a Ki of 377 nM and an inhibition rate of 62.8%. Additionally, M4mAChRModulator-2 can reverse the hyperlocomotion induced by Dizocilpine (MK-801) in mice and is applicable for schizophrenia research.

TC-N 22A is a strong, selective, oral active mGlu4 forward allosteric regulator (PAM) that can cross the blood-brain barrier. EC50 expression of TC-N 22A in BHK cells expressing human mGlu4 was 9 nM. TC-N 22A showed very low activity against mGlu 1, 2, 3, 5, and 7 receptors in excitation and forward allosteric models (EC50 >10 μM). TC-N 22A can be used in the study of central nervous system diseases.

VU0486321 is a potent mGlu1 PAM with moderate rat PK (CLp = 13.3. mL/min/kg,t1/2 = 54 min), good free fraction (human fu = 0.05, rat fu =0.03) and excellent CNS penetration (Kp = 1.02).

CB2R PAM is an orally active cannabinoid type 2 receptor (CB2Rs) positive allosteric modulator that enhances CP 55940 and 2-Arachidonylglycerol-stimulated [35S]GTPγS binding to CB2 receptors without affecting receptor activity in the absence of agonists. CB2R PAM shows anti-injury activity in a mouse model of neuropathic pain.

TRPC6-PAM-C20 is a selective TRPC6 positive allosteric modulator that induces a transient increase in intracellular Ca2+ with an EC50 of 2.37 μM in HEK cells expressing TRPC6 and enhances OAG-induced platelet aggregation.

CMPI hydrochloride, a potent and selective nAChR agonist, functions as a positive allosteric modulator (PAM) specifically targeting the α4:α4 subunit interface of the nAChR. It enhances the response of the (α4)3(β2)2 nAChR to acetylcholine (ACh) (10 μM) with an EC 50 of 0.26 μM. With its potential for researching nicotine dependence and various neuropsychiatric conditions linked to reduced brain cholinergic activity, CMPI hydrochloride stands as a significant compound in neurological research.

MMG-11 quarterhydrate is a potent and selective antagonist of human TLR2, inhibiting both TLR2/1 and TLR2/6 signaling with low cytotoxicity. The IC50 values for Pam3CSK4-induced hTLR2/1 and Pam2CSK4-induced hTLR2/6 responses are 1.7 μM and 5.7 μM, respectively [1].

Gentisuric acid, an Aspirin metabolite and a substrate of α-amidating monooxygenase (PAM), mitigates DNA damage induced by Mitomycin C. [1] [2]

MB327, a bipyridine nonoxime compound, enhances neuromuscular function by restoring the activity of nicotinamide acetylcholine receptors (nAChRs) against carbachol desensitization through a typical type II PAM approach. Additionally, MB327 is effective in neutralizing nerve agent poisoning [1] [2].

MitoBloCK-10 (3-fluoro-N'-[(E)-(5-nitrothiophen-2-yl)m) inhibits Tim44 binding to the precursor and to Hsp70.MitoBloCK-10 is the first small molecule modulator to attenuate protein-associated motor (PAM) complex activity.