HTL-9936
Based on 1 Customer Validation
HTL-9936 is an orally active partial agonist of muscarinic M1 receptor. HTL-9936 has an EC50 of 32 nM for human M1 receptor and an EC50 of 224 nM for human M4 receptor. HTL-9936 activates Gq/11 coupling, promotes inositol phosphate accumulation, ERK1/2 phosphorylation, β-arrestin recruitment and receptor internalization. HTL-9936 can be used in the research of Alzheimer's disease and schizophrenia.
For research use only. We do not sell to patients.
- Purity : 99.93%
- CAS No.: 1438242-59-1
- Formula: C20H35N3O3
- Molecular Weight:365.51
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Storage:
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[4]|
mAChR1 32 nM (EC50) |
mAChR4 224 nM (EC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | EC50 |
168.8 nM
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Stimulation of intracellular calcium mobilization in CHO cells stably expressing human M1 receptors assessed by FLIPR assay at 37°C.
Stimulation of intracellular calcium mobilization in CHO cells stably expressing human M1 receptors assessed by FLIPR assay at 37°C.
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30276808 |
| CHO | EC50 |
1161 nM
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Stimulation of pERK 1/2 (Thr202/Tyr204) signalling in CHO cells stably expressing human M1 receptors, measured using an HTRF kit after overnight serum starvation and 10 min agonist stimulation at 37°C.
Stimulation of pERK 1/2 (Thr202/Tyr204) signalling in CHO cells stably expressing human M1 receptors, measured using an HTRF kit after overnight serum starvation and 10 min agonist stimulation at 37°C.
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30276808 |
| CHO | EC50 |
631 nM
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Agonist activity measured via inositol phosphate (IP1) accumulation assay in CHO Flp-In cells stably expressing human M1 muscarinic acetylcholine receptor, incubated at 37°C for 45 min, with FRET signals normalized to acetylcholine-induced maximum response.
Agonist activity measured via inositol phosphate (IP1) accumulation assay in CHO Flp-In cells stably expressing human M1 muscarinic acetylcholine receptor, incubated at 37°C for 45 min, with FRET signals normalized to acetylcholine-induced maximum response.
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34822784 |
| CHO-K1 | EC50 |
32 nM
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Full agonist activity measured via pERK1/2 phosphorylation assay in CHO-K1 cells stably expressing human M1 muscarinic acetylcholine receptor, serum-starved overnight then stimulated for 5 min at 37°C, with phosphorylated ERK1/2 levels measured via AlphaScreen Surefire assay and normalized to acetylcholine-induced maximum response.
Full agonist activity measured via pERK1/2 phosphorylation assay in CHO-K1 cells stably expressing human M1 muscarinic acetylcholine receptor, serum-starved overnight then stimulated for 5 min at 37°C, with phosphorylated ERK1/2 levels measured via AlphaScreen Surefire assay and normalized to acetylcholine-induced maximum response.
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34822784 |
| CHO-K1 | EC50 |
398 nM
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Partial agonist activity measured via pERK1/2 phosphorylation assay in CHO-K1 cells stably expressing human M4 muscarinic acetylcholine receptor, serum-starved overnight then stimulated for 5 min at 37°C, with phosphorylated ERK1/2 levels measured via AlphaScreen Surefire assay and normalized to acetylcholine-induced maximum response.
Partial agonist activity measured via pERK1/2 phosphorylation assay in CHO-K1 cells stably expressing human M4 muscarinic acetylcholine receptor, serum-starved overnight then stimulated for 5 min at 37°C, with phosphorylated ERK1/2 levels measured via AlphaScreen Surefire assay and normalized to acetylcholine-induced maximum response.
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34822784 |
| CHO | EC50 |
79 nM
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Full agonist activity measured via label-free dynamic mass redistribution (DMR) assay in CHO cells expressing human M1 muscarinic acetylcholine receptor.
Full agonist activity measured via label-free dynamic mass redistribution (DMR) assay in CHO cells expressing human M1 muscarinic acetylcholine receptor.
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34822784 |
In Vitro
HTL-9936 (30 min) acts as a low-potency but high-efficacy partial agonist at native rat cortical M1 receptors, with an EC50 of 2-2.7 μM[1].
HTL-9936 (2 h) binds to human recombinant M1 receptor, with a Ki value of 9093 nM[1].
HTL-9936 potently stimulates calcium mobilization in CHO cells expressing human M1 receptors, with an EC50 of 168.8 nM[1].
HTL-9936 (10 min) stimulates the pERK signaling pathway in CHO cells expressing human M1 receptors, with an EC50 of 1161 nM[1].
HTL-9936 potently activates recombinant human M1 receptors (EC50 = 32 nM) and human M4 receptors (EC50 = 224 nM), but shows no activity against human M2 and M3 receptors[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | Cmax |
|---|---|---|---|
| Rat[6] | 3, 10, 30, 100 mg/kg | p.o. | 6400 ng/mL |
In Vivo
HTL-9936 (intravenous injection; 2-hour infusion) causes a transient, dose-dependent increase in blood pressure in purebred male Beagle dogs during intravenous infusion[6].
HTL-9936 (3 mg/kg) reverses scopolamine (HY-N0296)-induced cognitive impairment in rats, with an ED50 of 3 mg/kg[4].
HTL-9936 (10-100 mg/kg; i.p.) dose-dependently restores contextual fear conditioning impaired by Scopolamine in male C57BL/6J mice[6].
HTL-9936 (3-30 mg/kg; p.o.) dose-dependently reverses scopolamine-induced passive avoidance deficits in adult male Wistar rats[6].
HTL-9936 (3 mg/kg; p.o.) exerts an additive partial reversal effect on Scopolamine-induced passive avoidance deficits in adult male Wistar rats when combined with a sub-effective dose of Donepezil (HY-14566)[6].
HTL-9936 (10 mg/kg; p.o.) improves working memory in the rat novel object recognition model.
HTL-9936 (30 mg/kg; i.p.) improves fear conditioning learning and memory deficits in Tg37 mice, a prion disease model[6].
HTL-9936 (0.3-1 mg/kg, subcutaneous injection, once daily for 10 consecutive days) significantly improves visuospatial working memory in aged Beagle dogs[6].
HTL-9936 (0.3-3 mg/kg; subcutaneous injection) increases the δ wave power in resting-state electroencephalograms of adult male cynomolgus monkeys[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 8-12 weeks, scopolamine-induced contextual fear conditioning deficit model)[6]
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Dosage:10, 30, 100 mg/kg
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Administration:i.p.
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Result:Dose-dependently restored contextual-dependent fear learning and memory impaired by Scopolamine.
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Animal Model:Wistar (male, ~11 weeks, scopolamine-induced passive avoidance deficit model)[6]
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Dosage:3, 10, 30 mg/kg
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Administration:p.o.
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Result:Dose-dependently reversed Scopolamine-induced amnesia.
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Animal Model:Wistar (male, ~11 weeks, scopolamine-induced passive avoidance deficit model with sub-effective donepezil)[6]
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Dosage:3 mg/kg
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Administration:p.o.
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Result:Produced a significant partial reversal of Scopolamine-induced deficits when combined with sub-effective Donepezil, consistent with an additive effect.
Reached an estimated unbound brain concentration of 79 nM.
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Animal Model:Wistar (male, ~11 weeks, novel object recognition working memory model)[6]
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Dosage:3, 10, 30 mg/kg
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Administration:p.o.
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Result:Improved working memory at 10 mg/kg.
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Animal Model:Tg37 hemizygous (male, 9 weeks post-inoculation with Rocky Mountain Laboratory prions, prion-induced fear conditioning deficit model)[6]
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Dosage:30 mg/kg
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Administration:i.p.
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Result:Improved hippocampal-dependent contextual learning and memory, with treated mice showing 34% immobility compared to 13% in vehicle-treated mice.
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Animal Model:Beagle (male and female, > 8 years, delayed non-matching to position visual-spatial working memory model)[6]
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Dosage:0.3, 1, 2 mg/kg
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Administration:s.c.; once daily for 10 days
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Result:Significantly improved visual-spatial memory at 0.3 mg/kg and 1 mg/kg.
Produced an effect equivalent to that of Donepezil (1.5 mg/kg, p.o.) at 1 mg/kg.
Reached measured CSF concentrations of 13 nM at 0.3 mg/kg, 48 nM at 1 mg/kg, and 128 nM at 2 mg/kg.
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Animal Model:(male, 8-10 kg, 12-15 years old, quantitative EEG resting state network firing assessment)[6]
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Dosage:0.3, 3 mg/kg
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Administration:s.c.
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Result:Increased delta power in resting state EEG.
Reached predicted unbound brain concentrations of 20 nM at 0.3 mg/kg and 198 nM at 3 mg/kg.
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Animal Model:Wistar (male, 220-300 g, cardiovascular safety pharmacology assessment)[6]
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Dosage:3, 10, 30, 100 mg/kg
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Administration:p.o.
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Result:Caused a dose-dependent increase in heart rate and mean arterial blood pressure averaged over the 5-hour post-dose period, with no significant effects at 3 mg/kg.
Produced transient effects that returned to baseline as reagent exposure declined.
Chemical Information
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CAS No. 1438242-59-1
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Appearance Solid-liquid mixture
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Molecular Weight 365.51
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Formula C20H35N3O3
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Color Off-white to light yellow
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SMILES
CC1(CCC1)NC(C2CCN([C@@H]3CCN(CCC3)C(OCC)=O)CC2)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (273.59 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (290 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[3]. Nguyen HTM, et al. Opportunities and challenges for the development of M muscarinic receptor positive allosteric modulators in the treatment for neurocognitive deficits. British journal of pharmacology. 2024 Jul;181(14):2114-2142. [Content Brief]
[4]. Felder CC, et al. Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases. Neuropharmacology. 2018 Jul 01;136(Pt C):449-458. [Content Brief]
[5]. Johnson CR, et al. Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders. Biomedicines. 2022 Feb 07;10(2):398. [Content Brief]
[6]. Brown AJH, et al. From structure to clinic: Design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer's disease. Cell. 2021 Nov 24;184(24):5886-5901.e22. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7359 mL | 13.6795 mL | 27.3590 mL | 68.3976 mL |
| 5 mM | 0.5472 mL | 2.7359 mL | 5.4718 mL | 13.6795 mL | |
| 10 mM | 0.2736 mL | 1.3680 mL | 2.7359 mL | 6.8398 mL | |
| 15 mM | 0.1824 mL | 0.9120 mL | 1.8239 mL | 4.5598 mL | |
| 20 mM | 0.1368 mL | 0.6840 mL | 1.3680 mL | 3.4199 mL | |
| 25 mM | 0.1094 mL | 0.5472 mL | 1.0944 mL | 2.7359 mL | |
| 30 mM | 0.0912 mL | 0.4560 mL | 0.9120 mL | 2.2799 mL | |
| 40 mM | 0.0684 mL | 0.3420 mL | 0.6840 mL | 1.7099 mL | |
| 50 mM | 0.0547 mL | 0.2736 mL | 0.5472 mL | 1.3680 mL | |
| 60 mM | 0.0456 mL | 0.2280 mL | 0.4560 mL | 1.1400 mL | |
| 80 mM | 0.0342 mL | 0.1710 mL | 0.3420 mL | 0.8550 mL | |
| 100 mM | 0.0274 mL | 0.1368 mL | 0.2736 mL | 0.6840 mL |
HTL-9936 Related Classifications
HY-148961 Related Classifications
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