Adaptaquin | CAS#385786-48-1 | HIF-PHD enzyme inhibitor

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

MedKoo CAT#: 561218

CAS#: 385786-48-1

Description: Adaptaquin is a hydroxyquinoline inhibitor of HIF-PHD enzymes. Adaptaquin reduces neuronal death and behavioral deficits after intracerebral hemorrhage (ICH) in several rodent models without affecting total iron or zinc distribution in the brain.

Chemical Structure

Adaptaquin

CAS# 385786-48-1

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 561218
Name: Adaptaquin
CAS#: 385786-48-1
Chemical Formula: C21H16ClN3O2
Exact Mass: 377.09
Molecular Weight: 377.830
Elemental Analysis: C, 66.76; H, 4.27; Cl, 9.38; N, 11.12; O, 8.47

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 210
10mg	USD 350
50mg	USD 890
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: Adaptaquin

IUPAC/Chemical Name: 7-[(4-Chlorophenyl)[(3-hydroxy-2-pyridinyl)amino]methyl]-8-quinolinol

InChi Key: KKYHNYRUBSYTCZ-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H16ClN3O2/c22-15-8-5-14(6-9-15)18(25-21-17(26)4-2-12-24-21)16-10-7-13-3-1-11-23-19(13)20(16)27/h1-12,18,26-27H,(H,24,25)

SMILES Code: OC1=C2N=CC=CC2=CC=C1C(C3=CC=C(Cl)C=C3)NC4=NC=CC=C4O

Appearance: 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

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Product Data:

Product Data

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Biological target:	HIF-prolyl hydroxylase-2 (PHD2) inhibitor.
In vitro activity:	By contrast, cultures treated with 0.5, 1 and 5 μM AQ (Adaptaquin) displayed robust protection from 6-OHDA, both in cell numbers and morphology, with extensive neurite preservation (Fig. 1A,B). This study further confirmed protection by immunostaining phosphorylated (Ser139) histone H2A.X (PH2AX), an apoptotic marker. In cultures treated with 6-OHDA ± AQ (Fig. 1C), 6-OHDA alone induced a robust increase in nuclear PH2AX staining while co-treatment with 0.5 μM AQ blocked this response. Altogether, these results demonstrate that AQ prevents apoptosis of 6-OHDA-treated neuronal PC12 cells. Reference: Neurobiol Dis. 2020 Mar; 136: 104725. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545957/
In vivo activity:	Adaptaquin-treated mice, however, showed decreased edema 7 days after collagenase injection, likely because adaptaquin, in contrast to the conditional deletion of HIF-PHD isoforms, is available to target vascular and immune cells (fig. S7B). Mice with striatal hemorrhage showed a preference for ipsilateral turns because of deficits in the weight-balancing movements of the limbs contralateral to the injury, as well as spatial neglect. This preference was normalized in adaptaquin-treated mice as measured by the corner turn task (Fig. 4C; P < 0.01). Another behavior (tape removal task), which represents a form of sensory neglect, improved significantly in adaptaquin-treated mice 1 and 3 days after ICH (Fig. 4D; P < 0.05). Adaptaquin-induced behavioral improvements were associated with a reduction in the number of degenerating neurons in perihematomal and hematomal areas of the mouse striatum (Fig. 4, E to I; P < 0.001). Reference: Sci Transl Med. 2016 Mar 2; 8(328): 328ra29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341138/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	33.9	89.70
	DMSO:PBS (pH 7.2) (1:2)	0.3	0.87
	DMF	30.0	79.40

Preparing Stock Solutions

The following data is based on the product molecular weight 377.83 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. Aimé P, Karuppagounder SS, Rao A, Chen Y, Burke RE, Ratan RR, Greene LA. The drug adaptaquin blocks ATF4/CHOP-dependent pro-death Trib3 induction and protects in cellular and mouse models of Parkinson's disease. Neurobiol Dis. 2020 Mar;136:104725. doi: 10.1016/j.nbd.2019.104725. Epub 2020 Jan 3. PMID: 31911115; PMCID: PMC7545957. 2. Neitemeier S, Dolga AM, Honrath B, Karuppagounder SS, Alim I, Ratan RR, Culmsee C. Inhibition of HIF-prolyl-4-hydroxylases prevents mitochondrial impairment and cell death in a model of neuronal oxytosis. Cell Death Dis. 2016 May 5;7(5):e2214. doi: 10.1038/cddis.2016.107. PMID: 27148687; PMCID: PMC4917646. 3. Li K, Li T, Wang Y, Xu Y, Zhang S, Culmsee C, Wang X, Zhu C. Sex differences in neonatal mouse brain injury after hypoxia-ischemia and adaptaquin treatment. J Neurochem. 2019 Sep;150(6):759-775. doi: 10.1111/jnc.14790. Epub 2019 Jul 28. PMID: 31188470. 4. Karuppagounder SS, Alim I, Khim SJ, Bourassa MW, Sleiman SF, John R, Thinnes CC, Yeh TL, Demetriades M, Neitemeier S, Cruz D, Gazaryan I, Killilea DW, Morgenstern L, Xi G, Keep RF, Schallert T, Tappero RV, Zhong J, Cho S, Maxfield FR, Holman TR, Culmsee C, Fong GH, Su Y, Ming GL, Song H, Cave JW, Schofield CJ, Colbourne F, Coppola G, Ratan RR. Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models. Sci Transl Med. 2016 Mar 2;8(328):328ra29. doi: 10.1126/scitranslmed.aac6008. PMID: 26936506; PMCID: PMC5341138.
In vitro protocol:	1. Aimé P, Karuppagounder SS, Rao A, Chen Y, Burke RE, Ratan RR, Greene LA. The drug adaptaquin blocks ATF4/CHOP-dependent pro-death Trib3 induction and protects in cellular and mouse models of Parkinson's disease. Neurobiol Dis. 2020 Mar;136:104725. doi: 10.1016/j.nbd.2019.104725. Epub 2020 Jan 3. PMID: 31911115; PMCID: PMC7545957. 2. Neitemeier S, Dolga AM, Honrath B, Karuppagounder SS, Alim I, Ratan RR, Culmsee C. Inhibition of HIF-prolyl-4-hydroxylases prevents mitochondrial impairment and cell death in a model of neuronal oxytosis. Cell Death Dis. 2016 May 5;7(5):e2214. doi: 10.1038/cddis.2016.107. PMID: 27148687; PMCID: PMC4917646.
In vivo protocol:	1. Li K, Li T, Wang Y, Xu Y, Zhang S, Culmsee C, Wang X, Zhu C. Sex differences in neonatal mouse brain injury after hypoxia-ischemia and adaptaquin treatment. J Neurochem. 2019 Sep;150(6):759-775. doi: 10.1111/jnc.14790. Epub 2019 Jul 28. PMID: 31188470. 2. Karuppagounder SS, Alim I, Khim SJ, Bourassa MW, Sleiman SF, John R, Thinnes CC, Yeh TL, Demetriades M, Neitemeier S, Cruz D, Gazaryan I, Killilea DW, Morgenstern L, Xi G, Keep RF, Schallert T, Tappero RV, Zhong J, Cho S, Maxfield FR, Holman TR, Culmsee C, Fong GH, Su Y, Ming GL, Song H, Cave JW, Schofield CJ, Colbourne F, Coppola G, Ratan RR. Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models. Sci Transl Med. 2016 Mar 2;8(328):328ra29. doi: 10.1126/scitranslmed.aac6008. PMID: 26936506; PMCID: PMC5341138.

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1: Ratan RR. The Chemical Biology of Ferroptosis in the Central Nervous System. Cell Chem Biol. 2020 May 21;27(5):479-498. doi: 10.1016/j.chembiol.2020.03.007. Epub 2020 Apr 2. PMID: 32243811; PMCID: PMC7245561.

2: Aimé P, Karuppagounder SS, Rao A, Chen Y, Burke RE, Ratan RR, Greene LA. The drug adaptaquin blocks ATF4/CHOP-dependent pro-death Trib3 induction and protects in cellular and mouse models of Parkinson's disease. Neurobiol Dis. 2020 Mar;136:104725. doi: 10.1016/j.nbd.2019.104725. Epub 2020 Jan 3. PMID: 31911115; PMCID: PMC7545957.

3: Li K, Li T, Wang Y, Xu Y, Zhang S, Culmsee C, Wang X, Zhu C. Sex differences in neonatal mouse brain injury after hypoxia-ischemia and adaptaquin treatment. J Neurochem. 2019 Sep;150(6):759-775. doi: 10.1111/jnc.14790. Epub 2019 Jul 28. PMID: 31188470.

4: Vetrovoy O, Rybnikova E. Neuroprotective action of PHD inhibitors is predominantly HIF-1-independent: An Editorial for 'Sex differences in neonatal mouse brain injury after hypoxia-ischemia and adaptaquin treatment' on page 759. J Neurochem. 2019 Sep;150(6):645-647. doi: 10.1111/jnc.14822. Epub 2019 Aug 2. PMID: 31373011.

5: Poloznikov AA, Nikulin SV, Zakhariants AA, Khristichenko AY, Hushpulian DM, Gazizov IN, Tishkov VI, Gazaryan IG. "Branched Tail" Oxyquinoline Inhibitors of HIF Prolyl Hydroxylase: Early Evaluation of Toxicity and Metabolism Using Liver- on-a-chip. Drug Metab Lett. 2019;13(1):45-52. doi: 10.2174/1872312813666181129100950. PMID: 30488807.

6: David BT, Curtin JJ, Brown JL, Coutts DJC, Boles NC, Hill CE. Treatment with hypoxia-mimetics protects cultured rat Schwann cells against oxidative stress- induced cell death. Glia. 2021 Sep;69(9):2215-2234. doi: 10.1002/glia.24019. Epub 2021 May 21. PMID: 34019306.

7: Karuppagounder SS, Alim I, Khim SJ, Bourassa MW, Sleiman SF, John R, Thinnes CC, Yeh TL, Demetriades M, Neitemeier S, Cruz D, Gazaryan I, Killilea DW, Morgenstern L, Xi G, Keep RF, Schallert T, Tappero RV, Zhong J, Cho S, Maxfield FR, Holman TR, Culmsee C, Fong GH, Su Y, Ming GL, Song H, Cave JW, Schofield CJ, Colbourne F, Coppola G, Ratan RR. Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models. Sci Transl Med. 2016 Mar 2;8(328):328ra29. doi: 10.1126/scitranslmed.aac6008. PMID: 26936506; PMCID: PMC5341138.

8: Neitemeier S, Dolga AM, Honrath B, Karuppagounder SS, Alim I, Ratan RR, Culmsee C. Inhibition of HIF-prolyl-4-hydroxylases prevents mitochondrial impairment and cell death in a model of neuronal oxytosis. Cell Death Dis. 2016 May 5;7(5):e2214. doi: 10.1038/cddis.2016.107. PMID: 27148687; PMCID: PMC4917646.

9: Poloznikov AA, Nersisyan SA, Hushpulian DM, Kazakov EH, Tonevitsky AG, Kazakov SV, Vechorko VI, Nikulin SV, Makarova JA, Gazaryan IG. HIF Prolyl Hydroxylase Inhibitors for COVID-19 Treatment: Pros and Cons. Front Pharmacol. 2021 Jan 29;11:621054. doi: 10.3389/fphar.2020.621054. PMID: 33584306; PMCID: PMC7878396.

10: David BT, Curtin JJ, Brown JL, Scorpio K, Kandaswamy V, Coutts DJC, Vivinetto A, Bianchimano P, Karuppagounder SS, Metcalfe M, Cave JW, Hill CE. Temporary induction of hypoxic adaptations by preconditioning fails to enhance Schwann cell transplant survival after spinal cord injury. Glia. 2023 Mar;71(3):648-666. doi: 10.1002/glia.24302. Epub 2022 Dec 24. PMID: 36565279.

11: Wei GZ, Saraswat Ohri S, Khattar NK, Listerman AW, Doyle CH, Andres KR, Karuppagounder SS, Ratan RR, Whittemore SR, Hetman M. Hypoxia-inducible factor prolyl hydroxylase domain (PHD) inhibition after contusive spinal cord injury does not improve locomotor recovery. PLoS One. 2021 Apr 5;16(4):e0249591. doi: 10.1371/journal.pone.0249591. PMID: 33819286; PMCID: PMC8021188.

12: Poloznikov AA, Nikulin SV, Hushpulian DM, Khristichenko AY, Osipyants AI, Asachenko AF, Shurupova OV, Savin SS, Lee SH, Gaisina IN, Thatcher GRJ, Narciso A, Chang EP, Kazakov SV, Krucher N, Tishkov VI, Thomas B, Gazaryan IG. Structure-Activity Relationships and Transcriptomic Analysis of Hypoxia- Inducible Factor Prolyl Hydroxylase Inhibitors. Antioxidants (Basel). 2022 Jan 24;11(2):220. doi: 10.3390/antiox11020220. PMID: 35204103; PMCID: PMC8868400.

13: Osipyants AI, Poloznikov AA, Smirnova NA, Hushpulian DM, Khristichenko AY, Chubar TA, Zakhariants AA, Ahuja M, Gaisina IN, Thomas B, Brown AM, Gazaryan IG, Tishkov VI. L-ascorbic acid: A true substrate for HIF prolyl hydroxylase? Biochimie. 2018 Apr;147:46-54. doi: 10.1016/j.biochi.2017.12.011. Epub 2017 Dec 28. PMID: 29289682; PMCID: PMC6460286.

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