Sunvozertinib (DZD9008) is a potent ErbBs (EGFR, Her2, especially mutant) and BTK inhibitor. Sunvozertinib showed IC50s of 20.4, 20.4, 1.1, 7.5, and 80.4 nM for EGFR exon 20 NPH insertion, EGFR exon 20 ASV insertion, EGFR L858R and T790M mutations, and Her2 exon 20 YVMA and EGFR WT A431, respectively (Details For information, check and find patent WO2019149164A1, example 52).
On July 2, 2025, the Food and Drug Administration granted accelerated approval to sunvozertinib (Zegfrovy, Dizal (Jiangsu) Pharmaceutical Co., Ltd.) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

Physicochemical Properties

Molecular Formula	C29H35CLFN7O3
Molecular Weight	584.084708452225
Exact Mass	583.247
Elemental Analysis	C, 59.63; H, 6.04; Cl, 6.07; F, 3.25; N, 16.79; O, 8.22
CAS #	2370013-12-8
Related CAS #	(S)-Sunvozertinib;2370013-49-1
PubChem CID	139377809
Appearance	Off-white to light brown solid powder
LogP	5
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	10
Heavy Atom Count	41
Complexity	885
Defined Atom Stereocenter Count	1
SMILES	CC(C)(C1=CC(=C(C=C1NC2=NC(=NC=C2)NC3=C(C=C(C(=C3)NC(=O)C=C)N4CC[C@H](C4)N(C)C)OC)Cl)F)O
InChi Key	BTMKEDDEMKKSEF-QGZVFWFLSA-N
InChi Code	InChI=1S/C29H35ClFN7O3/c1-7-27(39)34-22-14-23(25(41-6)15-24(22)38-11-9-17(16-38)37(4)5)35-28-32-10-8-26(36-28)33-21-13-19(30)20(31)12-18(21)29(2,3)40/h7-8,10,12-15,17,40H,1,9,11,16H2,2-6H3,(H,34,39)(H2,32,33,35,36)/t17-/m1/s1
Chemical Name	N-{5-({4-[5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)anilino]pyrimidin-2-yl}amino)-2-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-4-methoxyphenyl}prop-2-enamide
Synonyms	DZD-9008; Sunvozertinib; DZD 9008; sunvozertinib; 2370013-12-8; Sunvozertinib [INN]; L1Q2K5JYO8; DZD9008
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	ErbBs/epidermal growth factor receptor (EGFR) exon 20 insertion mutations; BTK
ln Vitro	Sunvozertinib's GI50 values were 60.4, 83.2, 3.3, 101.3, and 47.1 nM A431, respectively, against the EGFR exon NPH insertion, EGFR exon 20 ASV insertion, EGFR L858R and T790M mutations, Her2 Exon20 YVMA, and EGFR WT. For BTK WT OCI -LY-10, BTK WT TMD-8, BTK WT Ri-1, and non-BCR activated DB, the GI50 of sunvozertinib was 3.2, 5.8, 51.3, and 1983.5 nM, respectively [1]. p-BTK is inhibited by sunvozertinib at an IC50 of 1.6 nM[1].
Toxicity/Toxicokinetics	The prescribing information for taletrectinib includes warnings and precautions for hepatotoxicity, interstitial lung disease/pneumonitis, QTc interval prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, skeletal fractures, and embryo-fetal toxicity. The recommended taletrectinib dose is 600 mg orally once daily on an empty stomach (no food intake at least 2 hours before and 2 hours after taking taletrectinib) until disease progression or unacceptable toxicity.
References	[1]. Erbb/btk inhibitors. WO2019149164A1.
Additional Infomation	Sunvozertinib is an orally available, irreversible, dual kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) that shows similar activity against certain activating mutations, including exon 20 insertions (exon20ins), with potential antineoplastic activity. Upon oral administration,sunvozertinib binds to and inhibits EGFR and HER2, which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. EGFR and HER2 are receptor tyrosine kinases that play major roles in tumor cell proliferation and tumor vascularization. In contrast to other agents active against exon20ins mutations, sunvozertinib appears to be more selective against mutated EGFR than wild-type (wt) EGFR. This may lessen wtEGFR-related dose-limiting toxicity and may allow for the administration of the desired therapeutic dose of sunvozertinib. Drug Indication Treatment of non-small cell lung cancer Efficacy was evaluated in patients with locally advanced or metastatic, ROS1-positive NSCLC enrolled in two multicenter, single-arm, open-label clinical trials, TRUST-I (NCT04395677) and TRUST-II (NCT04919811). The efficacy population included 157 patients (103 in TRUST-I; 54 in TRUST-II) who were naïve to treatment with a ROS1 tyrosine kinase inhibitor (TKI) and 113 patients (66 in TRUST-I; 47 in TRUST-II) who had received one prior ROS1 TKI. Patients may have received prior chemotherapy for advanced disease. The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR), determined by blinded independent central review according to RECIST v1.1. For treatment-naive patients, ORR was 90% (95% CI: 83, 95) in TRUST-I and 85% (95% CI: 73, 93) in TRUST-II, with 72% and 63% of responders having a DOR ≥12 months, respectively. For TKI-pretreated patients, ORR was 52% (95% CI: 39, 64) in TRUST-I and 62% (95% CI: 46, 75) in TRUST-II, with 74% and 83% of responders having a DOR ≥6 months, respectively.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~85.60 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.28 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7121 mL	8.5605 mL	17.1209 mL
	5 mM	0.3424 mL	1.7121 mL	3.4242 mL
	10 mM	0.1712 mL	0.8560 mL	1.7121 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.