PZM21 | PZM-21 | CAS# 1997387-43-5 | Gi Activator

MedKoo Cat#: 526831 | Name: PZM21

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PZM21 is a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. PZM21 is an experimental opioid analgesic drug that is being researched for the treatment of pain. It is a functionally selective μ-opioid receptor agonist which produces μ-opioid receptor mediated G protein signaling, with potency and efficacy similar to morphine, but with less β-arrestin 2 recruitment. In tests on mice, PZM21 was slightly less potent than morphine or TRV130 as an analgesic, but also had significantly reduced adverse effects, with less constipation than morphine, and very little respiratory depression, even at high doses.

Chemical Structure

PZM21

CAS#1997387-43-5 (free base)

Theoretical Analysis

MedKoo Cat#: 526831

Name: PZM21

CAS#: 1997387-43-5 (free base)

Chemical Formula: C19H27N3O2S

Exact Mass: 361.1824

Molecular Weight: 361.50

Elemental Analysis: C, 63.13; H, 7.53; N, 11.62; O, 8.85; S, 8.87

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,750.00	Ready to ship
2g	USD 6,250.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1997387-43-5 (free base) 2287250-29-5 (HCl) 2287246-62-0 (sulfate)

Synonym

PZM21; PZM-21; PZM 21

IUPAC/Chemical Name

1-[(2S)-2-(Dimethylamino)-3-(4-hydroxyphenyl)propyl]-3-[(2S)-1-(thiophen-3-yl)propan-2-yl]urea

InChi Key

MEDBIJOVZJEMBI-YOEHRIQHSA-N

InChi Code

InChI=1S/C19H27N3O2S/c1-14(10-16-8-9-25-13-16)21-19(24)20-12-17(22(2)3)11-15-4-6-18(23)7-5-15/h4-9,13-14,17,23H,10-12H2,1-3H3,(H2,20,21,24)/t14-,17-/m0/s1

SMILES Code

O=C(N[C@@H](C)CC1=CSC=C1)NC[C@@H](N(C)C)CC2=CC=C(O)C=C2

Appearance

White to off-white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C9R10B08

View CoA: current batch, Lot#A8T07K20

View CoA: current batch, Lot#A8T08K03

QC Data

View QC data: current batch, Lot#C9R10B08

View QC data: current batch, Lot#A8T07K20

View QC data: current batch, Lot#A8T08K03

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PZM21 is a μ opioid receptor agonist with an EC50 of 1.8 nM.

In vitro activity:

In HEK 293 cells expressing μ receptors, PZM21 (10−9 – 3 × 10−5 M) produced concentration-dependent Gi activation (Figure 1A and Table 1). The responses evoked by PZM21 were compared to those evoked by two well-characterized μ receptor ligands, DAMGO (high efficacy agonist) and morphine (lower efficacy agonist) in the same assay. Examination of the maximum response produced by each agonist (an indication of agonist efficacy) (Table 1) revealed that under the assay conditions, PZM21 and morphine were partial agonists for Gi activation with significantly lower efficacy than DAMGO. In the arrestin-3 recruitment assay PZM21 (10−9 – 3 × 10−5 M) produced a small but measurable amount of arrestin recruitment (Figure 1B). The maximum responses to PZM21 and morphine were lower than that of DAMGO whereas PZM21 and morphine were not significantly different. Reference: Br J Pharmacol. 2018 Jul;175(13):2653-2661. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003631/

In vivo activity:

In C57/BL mice breathing air, PZM21 (40 mg·kg−1 injected s.c.) caused significant respiratory depression (Figure 2B) that was rapid in onset, the peak effect being attained 10 – 15 min after injecting the drug, and persisted for the duration of the 30 min post injection observation period. In mice breathing air, respiration gradually declines with time; animals also sometimes curl up ‘asleep’ which interferes with plethysmograph recording. To circumvent this, experiments were performed in which mice breathe 5% CO2 in air. This increases MV (minute volume) which in saline-treated mice remains constant for periods of up to 90 min (Figure 2D). In CD-1 mice breathing 5% CO2 in air, the respiratory depression induced by PZM21 (10 – 40 mg·kg−1 i.p.) was dose-dependent and was maintained over the 60 min period following drug administration (Figure 2D, E). Reference: Br J Pharmacol. 2018 Jul;175(13):2653-2661. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003631/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	276.63
	Ethanol	10.0	27.70

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 361.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Ma M, Sun J, Li M, Yu Z, Cheng J, Zhong B, Shi W. Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists. Molecules. 2019 Jan 11;24(2):259. doi: 10.3390/molecules24020259. PMID: 30641969; PMCID: PMC6359544. 2. Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G. The novel μ-opioid receptor agonist PZM21 depresses respiration and induces tolerance to antinociception. Br J Pharmacol. 2018 Jul;175(13):2653-2661. doi: 10.1111/bph.14224. Epub 2018 May 14. PMID: 29582414; PMCID: PMC6003631. 3. Kudla L, Bugno R, Skupio U, Wiktorowska L, Solecki W, Wojtas A, Golembiowska K, Zádor F, Benyhe S, Buda S, Makuch W, Przewlocka B, Bojarski AJ, Przewlocki R. Functional characterization of a novel opioid, PZM21, and its effects on the behavioural responses to morphine. Br J Pharmacol. 2019 Dec;176(23):4434-4445. doi: 10.1111/bph.14805. Epub 2019 Dec 8. PMID: 31347704; PMCID: PMC6932942.

In vitro protocol:

In vivo protocol:

1. Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G. The novel μ-opioid receptor agonist PZM21 depresses respiration and induces tolerance to antinociception. Br J Pharmacol. 2018 Jul;175(13):2653-2661. doi: 10.1111/bph.14224. Epub 2018 May 14. PMID: 29582414; PMCID: PMC6003631. 2. Kudla L, Bugno R, Skupio U, Wiktorowska L, Solecki W, Wojtas A, Golembiowska K, Zádor F, Benyhe S, Buda S, Makuch W, Przewlocka B, Bojarski AJ, Przewlocki R. Functional characterization of a novel opioid, PZM21, and its effects on the behavioural responses to morphine. Br J Pharmacol. 2019 Dec;176(23):4434-4445. doi: 10.1111/bph.14805. Epub 2019 Dec 8. PMID: 31347704; PMCID: PMC6932942.

1: Singleton S, Dieterle C, Walker DJ, Runeberg T, Oswald AS, Rosenqvist G, Robertson L, McCarthy T, Sarkar S, Baptista-Hon D, Hales TG. Activation of μ receptors by SR-17018 through a distinctive mechanism. Neuropharmacology. 2024 Nov 1;258:110093. doi: 10.1016/j.neuropharm.2024.110093. Epub 2024 Jul 25. PMID: 39067665. 2: Guo Y, Yu R, Zhang T, Ren F, Yu Z, Cheng J, Jia H, Shi W, Zhang Y. Synthesis and Biological Evaluation of Novel Biased Mu-Opioid Receptor Agonists. Molecules. 2024 Jun 21;29(13):2961. doi: 10.3390/molecules29132961. PMID: 38998913; PMCID: PMC11243066. 3: Nerurkar A, Nguyen T, Wang S, Bhatt U, Li K, Li Y, Ding P, Seidl FJ, Holan M, Lee J, Widjaja T, Wei ZL, Sadlowski C, Sperandio D, McGee LR, Youngblood B, Schwartz N, Gehlert D, Medina JC. Novel series of tunable µOR modulators with enhanced brain penetration for the treatment of opioid use disorder, pain and neuropsychiatric indications. Bioorg Med Chem Lett. 2023 Aug 15;92:129405. doi: 10.1016/j.bmcl.2023.129405. Epub 2023 Jul 5. PMID: 37414346; PMCID: PMC10529836. 4: Szumiec L, Bugno R, Szumiec L, Przewlocki R. The differential influence of PZM21, a nonrewarding μ-opioid receptor agonist with G protein bias, on behavioural despair and fear response in mice. Behav Brain Res. 2023 Jul 9;449:114466. doi: 10.1016/j.bbr.2023.114466. Epub 2023 May 3. PMID: 37146718. 5: Huang KH, Morato NM, Feng Y, Cooks RG. High-Throughput Diversification of Complex Bioactive Molecules by Accelerated Synthesis in Microdroplets. Angew Chem Int Ed Engl. 2023 May 22;62(22):e202300956. doi: 10.1002/anie.202300956. Epub 2023 Apr 20. PMID: 36941213; PMCID: PMC10182919. 6: Paul B, Sribhashyam S, Majumdar S. Opioid signaling and design of analgesics. Prog Mol Biol Transl Sci. 2023;195:153-176. doi: 10.1016/bs.pmbts.2022.06.017. Epub 2022 Aug 5. PMID: 36707153; PMCID: PMC10325139. 7: Zhuang Y, Wang Y, He B, He X, Zhou XE, Guo S, Rao Q, Yang J, Liu J, Zhou Q, Wang X, Liu M, Liu W, Jiang X, Yang D, Jiang H, Shen J, Melcher K, Chen H, Jiang Y, Cheng X, Wang MW, Xie X, Xu HE. Molecular recognition of morphine and fentanyl by the human μ-opioid receptor. Cell. 2022 Nov 10;185(23):4361-4375.e19. doi: 10.1016/j.cell.2022.09.041. PMID: 36368306. 8: Li X, Guo Y, Li J, Yu Z, Cheng J, Ren F, Jia H, Zhang Y, Cui S, Zhang T, Shi W. Discovery and Structural Explorations of G-Protein Biased μ-Opioid Receptor Agonists. ChemMedChem. 2022 Dec 16;17(24):e202200416. doi: 10.1002/cmdc.202200416. Epub 2022 Oct 28. PMID: 36210341. 9: Jung JH, Jang IH, Kim YO, Kim S, Yoon MH, Kim YC. Discovery of pyrazole-1-carboxamide derivatives as novel Gi-biased μ-opioid receptor agonists. Drug Dev Res. 2022 Nov;83(7):1600-1612. doi: 10.1002/ddr.21980. Epub 2022 Sep 20. PMID: 36124859. 10: Zádor F, Király K, Essmat N, Al-Khrasani M. Recent Molecular Insights into Agonist-specific Binding to the Mu-Opioid Receptor. Front Mol Biosci. 2022 Jun 13;9:900547. doi: 10.3389/fmolb.2022.900547. PMID: 35769909; PMCID: PMC9234319. 11: Wang H, Hetzer F, Huang W, Qu Q, Meyerowitz J, Kaindl J, Hübner H, Skiniotis G, Kobilka BK, Gmeiner P. Structure-Based Evolution of G Protein-Biased μ-Opioid Receptor Agonists. Angew Chem Int Ed Engl. 2022 Jun 27;61(26):e202200269. doi: 10.1002/anie.202200269. Epub 2022 Apr 29. PMID: 35385593; PMCID: PMC9322534. 12: Noble F, Marie N. Biased Opioid Ligands: Revolution or Evolution? Front Pain Res (Lausanne). 2021 Sep 24;2:722820. doi: 10.3389/fpain.2021.722820. PMID: 35295469; PMCID: PMC8915667. 13: Kudla L, Bugno R, Podlewska S, Szumiec L, Wiktorowska L, Bojarski AJ, Przewlocki R. Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies. Pharmaceutics. 2021 Dec 27;14(1):55. doi: 10.3390/pharmaceutics14010055. PMID: 35056950; PMCID: PMC8779292. 14: Stahl EL, Bohn LM. Low Intrinsic Efficacy Alone Cannot Explain the Improved Side Effect Profiles of New Opioid Agonists. Biochemistry. 2022 Sep 20;61(18):1923-1935. doi: 10.1021/acs.biochem.1c00466. Epub 2021 Sep 1. PMID: 34468132; PMCID: PMC8885792. 15: Lee JH, Shon SY, Jeon W, Hong SJ, Ban J, Lee DS. Discovery of μ,δ-Opioid Receptor Dual-Biased Agonists That Overcome the Limitation of Prior Biased Agonists. ACS Pharmacol Transl Sci. 2021 Apr 6;4(3):1149-1160. doi: 10.1021/acsptsci.1c00044. PMID: 34151205; PMCID: PMC8204323. 16: Kuppalli S, Seth R, Orhurhu V, Urits I, Kaye AD, Hunter C, Gulati A, Adekoya P, Kaye AM, Jones MR. Recent Advances in the Treatment of Opioid Use Disorder. Curr Pain Headache Rep. 2021 Mar 11;25(4):23. doi: 10.1007/s11916-021-00941-8. PMID: 33693999. 17: Singleton S, Baptista-Hon DT, Edelsten E, McCaughey KS, Camplisson E, Hales TG. TRV130 partial agonism and capacity to induce anti-nociceptive tolerance revealed through reducing available μ-opioid receptor number. Br J Pharmacol. 2021 Apr;178(8):1855-1868. doi: 10.1111/bph.15409. Epub 2021 Mar 2. PMID: 33555037. 18: Liao S, Tan K, Floyd C, Bong D, Pino MJ Jr, Wu C. Probing biased activation of mu-opioid receptor by the biased agonist PZM21 using all atom molecular dynamics simulation. Life Sci. 2021 Mar 15;269:119026. doi: 10.1016/j.lfs.2021.119026. Epub 2021 Jan 11. PMID: 33444617. 19: Jiang X, Li S, Zhang H, Wang LL. Discovery of potentially biased agonists of mu-opioid receptor (MOR) through molecular docking, pharmacophore modeling, and MD simulation. Comput Biol Chem. 2021 Feb;90:107405. doi: 10.1016/j.compbiolchem.2020.107405. Epub 2020 Nov 1. PMID: 33184004. 20: Podlewska S, Bugno R, Kudla L, Bojarski AJ, Przewlocki R. Molecular Modeling of µ Opioid Receptor Ligands with Various Functional Properties: PZM21, SR-17018, Morphine, and Fentanyl-Simulated Interaction Patterns Confronted with Experimental Data. Molecules. 2020 Oct 12;25(20):4636. doi: 10.3390/molecules25204636. PMID: 33053718; PMCID: PMC7594085.