AZD-5597
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406328

CAS#: 924641-59-8

Description: AZD-5597 is potent CDK inhibitor with in vitro anti-proliferative effects against a range of cancer cell lines. AZD-5597 has excellent physiochemical properties and large margins against inhibition of CYP isoforms and the hERG ion channel.

Chemical Structure

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AZD-5597
CAS# 924641-59-8
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406328
Name: AZD-5597
CAS#: 924641-59-8
Chemical Formula: C23H28FN7O
Exact Mass: 437.23
Molecular Weight: 437.513
Elemental Analysis: C, 63.14; H, 6.45; F, 4.34; N, 22.41; O, 3.66

Price and Availability

Size Price Availability Quantity
5mg USD 120 Ready to ship
10mg USD 200 Ready to ship
25mg USD 450 Ready to ship
50mg USD 750 Ready to ship
100mg USD 1250 Ready to ship
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Synonym: AZD5597; AZD 5597; AZD-5597

IUPAC/Chemical Name: (S)-(4-((5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-yl)amino)phenyl)(3-(methylamino)pyrrolidin-1-yl)methanone

InChi Key: NTSDIJMNXYJJNG-SFHVURJKSA-N

InChi Code: InChI=1S/C23H28FN7O/c1-14(2)31-15(3)26-12-20(31)21-19(24)11-27-23(29-21)28-17-7-5-16(6-8-17)22(32)30-10-9-18(13-30)25-4/h5-8,11-12,14,18,25H,9-10,13H2,1-4H3,(H,27,28,29)/t18-/m0/s1

SMILES Code: O=C(C1=CC=C(NC2=NC=C(F)C(C3=CN=C(C)N3C(C)C)=N2)C=C1)N4C[C@@H](NC)CC4

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, not in water

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:         

Biological target: AZD-5597 is a CDK1, CDK2, and LoVo inhibitor with an IC50 of 0.002, 0.002, and 0.039 μM respectively.
In vitro activity: Much improved levels of potency against CDK1 were observed for (S)-3-methylamine pyrrolidines. Again, varying levels of anti-proliferative activity were seen with 5-fluoro versus 5-H pyrimidine substitution. The best balance of CDK1/2 enzyme and anti-proliferative activity was observed with the more lipophilic 5-fluoropyrimidine (S)-methylamine, (S)-15b (AZD-5597). With high levels of both enzyme potency and cellular anti-proliferative activity, this promising compound was progressed into additional physiochemical assays (Table 5). The overall profile of (S)-15b indicated that it was suitable for further development as an iv agent. The high margins against hERG allow for flexibility in dosing either as a bolus or by extended infusions. The lack of CYP inhibition lowers the risk of problematic drug–drug interactions in the clinic. Excellent aqueous solubility from crystalline (S)-15b was obtained, even in simple saline formulations. In addition, the formulated drug showed no significant decomposition on exposure to light, plasma or through chemical hydrolysis. Reference: Bioorg Med Chem Lett. 2008 Dec 15;18(24):6369-73. https://www.sciencedirect.com/science/article/pii/S0960894X08012894?via%3Dihub
In vivo activity: (S)-15b (AZD-5597) possessed good pharmacokinetic parameters with moderate to low clearance in nude mouse and rat (Table 6). Clearance in the dog was higher (58% liver blood flow), due to the higher levels of free drug in dog plasma, but was still acceptable for an intravenously dosed drug. Nude mice were implanted subcutaneously with SW620 human colon adenocarcinoma cells and in vivo tumour xenograft efficacy was established by dosing (S)-15b intraperitoneally (ip). Anti-tumour activity was observed with an inhibition of tumour volume of 55% (P < 0.001) when dosed intermittently (Monday, Wednesday, Friday) for 3 weeks at 15 mg/kg. On the basis of data presented, the compound (S)-15b was selected for further development as AZD5597. Reference: Bioorg Med Chem Lett. 2008 Dec 15;18(24):6369-73. https://www.sciencedirect.com/science/article/pii/S0960894X08012894?via%3Dihub

Preparing Stock Solutions

The following data is based on the product molecular weight 437.51 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.

Recalculate based on batch purity %
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. Jones CD, Andrews DM, Barker AJ, Blades K, Daunt P, East S, Geh C, Graham MA, Johnson KM, Loddick SA, McFarland HM, McGregor A, Moss L, Rudge DA, Simpson PB, Swain ML, Tam KY, Tucker JA, Walker M. The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6369-73. doi: 10.1016/j.bmcl.2008.10.102. Epub 2008 Oct 25. PMID: 18996007.
In vitro protocol: 1. Jones CD, Andrews DM, Barker AJ, Blades K, Daunt P, East S, Geh C, Graham MA, Johnson KM, Loddick SA, McFarland HM, McGregor A, Moss L, Rudge DA, Simpson PB, Swain ML, Tam KY, Tucker JA, Walker M. The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6369-73. doi: 10.1016/j.bmcl.2008.10.102. Epub 2008 Oct 25. PMID: 18996007.
In vivo protocol: 1. Jones CD, Andrews DM, Barker AJ, Blades K, Daunt P, East S, Geh C, Graham MA, Johnson KM, Loddick SA, McFarland HM, McGregor A, Moss L, Rudge DA, Simpson PB, Swain ML, Tam KY, Tucker JA, Walker M. The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6369-73. doi: 10.1016/j.bmcl.2008.10.102. Epub 2008 Oct 25. PMID: 18996007.

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1. Inhibitors of protein kinase CDK9 for the treatment of NUT midline carcinomas. By Choidas, Axel; Klebl, Bert; Habenberger, Peter; Eickhoff, Jan; Thomas, Roman; Heuckmann, Johannes. From PCT Int. Appl. (2013), WO 2013026874 A1 20130228,

2. Susceptibility of tumor cells to selective CDK9 kinase inhibitors for predicting treatment of NUT midline carcinoma. By Choidas, Axel; Klebl, Bert; Habenberger, Peter; Eickhoff, Jan; Thomas, Roman; Heuckmann, Johannes. From PCT Int. Appl. (2013), WO 2013026890 A1 20130228,

3. Susceptibility of tumor cells to selective CDK9 kinase inhibitors for predicting treatment of NUT midline carcinoma. By Choidas, Axel; Klebl, Bert; Habenberger, Peter; Eickhoff, Jan; Thomas, Roman; Heuckmann, Johannes. From Eur. Pat. Appl. (2013), EP 2562265 A1 20130227,

4. Inhibitors of protein kinase CDK9 for the treatment of NUT midline carcinomas. By Choidas, Axel; Klebl, Bert; Habenberger, Peter; Eickhoff, Jan; Thomas, Roman; Heckmann, Johannes. From Eur. Pat. Appl. (2013), EP 2561867 A1 20130227,

5. Development of in silico models for pyrazoles and pyrimidine derivatives as cyclin-dependent kinase 2 inhibitors. By Wang, Fangfang; Ma, Zhi; Li, Yan; Zhu, Shanna; Xiao, Zhengtao; Zhang, Hong; Wang, Yonghua. From Journal of Molecular Graphics & Modelling (2011), 30, 67-81. ,

6. The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing. By Jones, Clifford D.; Andrews, David M.; Barker, Andrew J.; Blades, Kevin; Daunt, Paula; East, Simon; Geh, Catherine; Graham, Mark A.; Johnson, Keith M.; Loddick, Sarah A.; et al. From Bioorganic & Medicinal Chemistry Letters (2008), 18(24), 6369-6373. ,

7. Preparation of imidazolyl-pyrimidine compounds as CDK2 inhibitors. By Andrews, David; Finlay, Maurice Raymond; Green, Clive; Jones, Clifford. From PCT Int. Appl. (2007), WO 2007015064 A1 20070208,