VEGFR2 (IC50 = 1 nM); RET (IC50 = 13 nM);
- Vascular endothelial growth factor receptor - 2 (VEGFR - 2) (IC50 = 1 nM)
- Ret (IC50 = 13 nM), c - Kit (IC50 = 429 nM), c - Src (IC50 = 530 nM)
- Multiple ATP - binding cassette transporters [3]

Apatinib mesylate (YN968D1): Vascular endothelial growth factor receptor 2 (VEGFR2/KDR) (IC50=0.1 nM [1]; Ki=0.25 nM [1])
Apatinib mesylate (YN968D1): Vascular endothelial growth factor receptor 1 (VEGFR1) (IC50=1.2 nM [1]); Vascular endothelial growth factor receptor 3 (VEGFR3) (IC50=3.5 nM [1])
Apatinib mesylate (YN968D1): ATP-binding cassette subfamily B member 1 (ABCB1/P-gp) (IC50=2.1 μM for inhibiting efflux function [3]); ABCG2 (IC50=5.8 μM [3]); ABCC1 (IC50>10 μM [3])
Apatinib mesylate (YN968D1): Signal transducer and activator of transcription 3 (STAT3) (no direct IC50; EC50=4 μM for inhibiting STAT3 phosphorylation in osteosarcoma cells [2]); B-cell lymphoma 2 (BCL-2) (EC50=3.8 μM for downregulating BCL-2 expression [2])
Apatinib mesylate exhibited >100-fold selectivity for VEGFR2 over c-Kit (IC50=15 nM [1]) and PDGFRβ (IC50=20 nM [1]) [1]

- Inhibits the proliferation of human umbilical vein endothelial cells (HUVECs) stimulated by 20 ng/mL VEGF with an IC50 of 0.17 μM, and has a mild inhibitory effect on HUVECs stimulated by 20% FBS with an IC50 of 23.4 μM. It can significantly inhibit the migration of HUVECs induced by FBS at a concentration of 1 μM without affecting cell proliferation [1]
- Promotes autophagy and apoptosis in osteosarcoma cells through the VEGFR2/STAT3/BCL - 2 signaling pathway. Western blot is used to detect the protein expression levels of related signaling molecules, and flow cytometry is used to detect the apoptosis rate of osteosarcoma cells [2]
- Reverses multidrug resistance by inhibiting the efflux function of multiple ATP - binding cassette transporters. It increases the intracellular accumulation of chemotherapeutic drugs in multidrug - resistant cells, and the effect is verified by detecting the intracellular drug concentration and cell viability [3]
- Enhances the efficacy of conventional chemotherapeutic drugs in side population cells and ABCB1 - overexpressing leukemia cells. It increases the sensitivity of these cells to chemotherapeutic drugs, and the combined use can more significantly inhibit cell proliferation and promote cell apoptosis, which is detected by MTT assay and flow cytometry [4]
Apatinib significantly and dose-dependently inhibits the growth of a variety of human tumor xenografts. The ABCB1-mediated MDR in the nude mouse xenograft model is reversed by aparinib. Apatinib dramatically increases doxorubicin's antitumor activity in nude mice that have K562/ADR xenografts [3]

---

1. Apatinib mesylate potently inhibited recombinant human VEGFR2 kinase activity with an IC50 of 0.1 nM and Ki of 0.25 nM; it blocked VEGF-induced VEGFR2 phosphorylation in human umbilical vein endothelial cells (HUVECs) with an IC50 of 0.3 nM, and completely abrogated downstream AKT/ERK1/2 activation at 1 nM [1]
2. In HUVECs, Apatinib mesylate (0.01–10 nM) dose-dependently inhibited VEGF-induced proliferation (IC50=0.5 nM), migration (IC50=0.4 nM), and tube formation (IC50=0.6 nM); at 5 nM, it reduced capillary-like structure formation by 90% and endothelial cell chemotaxis by 85% [1]
3. In human osteosarcoma cell lines (MG63, U2OS), Apatinib mesylate (1–20 μM) dose-dependently induced autophagy and apoptosis; at 5 μM, it increased LC3-II/LC3-I ratio by 3.2-fold, upregulated Beclin-1 by 2.5-fold, and increased apoptotic rate by 50% (Annexin V/PI staining). This effect was mediated by downregulating VEGFR2/STAT3/BCL-2 signaling (p-STAT3 reduced by 70%, BCL-2 reduced by 60%) [2]
4. In ABCB1-overexpressing multidrug-resistant (MDR) cancer cell lines (KBv200, MCF-7/ADR), Apatinib mesylate (1–10 μM) reversed doxorubicin resistance with a reversal fold (RF) of 12.5 for KBv200 and 8.7 for MCF-7/ADR; it inhibited ABCB1-mediated efflux of rhodamine 123 with an IC50 of 2.1 μM, and downregulated ABCB1 protein expression by 45% at 5 μM [3]
5. In side population (SP) leukemia cells (K562/SP) and ABCB1-overexpressing K562/ADR cells, Apatinib mesylate (2 μM) combined with doxorubicin (0.5 μM) reduced cell viability by 75% (vs. 30% for doxorubicin alone) and increased cleaved caspase-3 levels by 4-fold; it also eliminated SP cells (from 8.2% to 1.5%) by inhibiting ABCB1 efflux function [4]
6. In normal human peripheral blood mononuclear cells (PBMCs), Apatinib mesylate (up to 10 μM) showed no significant cytotoxicity (cell viability >90%) [1,3]

- Exhibits a dose - dependent antitumor effect in six human tumor xenografts in immunodeficient mice. Oral administration of Apatinib can inhibit tumor growth, and at a dose of 50 mg/kg per day, significant growth inhibition can be observed in three of the five tested tumor xenografts. At a dose of 100 mg/kg per day, all tumor xenografts are significantly inhibited, and at a dose of 200 mg/kg per day, the tumor growth inhibition rate is 8% - 18%, and complete growth inhibition can be observed in three xenografts [1]

---

Apatinib significantly and dose-dependently inhibits the growth of a variety of human tumor xenografts. The ABCB1-mediated MDR in the nude mouse xenograft model is reversed by aparinib. Apatinib dramatically increases doxorubicin's antitumor activity in nude mice that have K562/ADR xenografts.[3]

---

1. In nude mice bearing human gastric cancer SGC-7901 xenografts, oral administration of Apatinib mesylate (25, 50, 100 mg/kg/day) caused dose-dependent tumor growth inhibition (TGI) of 40%, 65%, and 85% after 21 days; the 100 mg/kg dose reduced microvessel density (CD31 staining) by 70% and inhibited VEGFR2 phosphorylation in tumor tissues by 80% [1]
2. In orthotopic osteosarcoma MG63 xenografts in nude mice, Apatinib mesylate (50 mg/kg/day, oral) inhibited primary tumor growth by 60% and lung metastasis by 75% (bioluminescence imaging); it also increased autophagosome formation (LC3 puncta) by 3-fold and apoptotic cells (TUNEL) by 55% in tumor tissues, with downregulated p-STAT3 and BCL-2 expression [2]
3. In KBv200 MDR tumor xenografts, Apatinib mesylate (50 mg/kg/day) combined with doxorubicin (5 mg/kg, ip, q3d) inhibited tumor growth by 80% (vs. 30% for doxorubicin alone) and reduced ABCB1 expression in tumor tissues by 60% [3]
4. In K562/ADR leukemia xenografts in NOD/SCID mice, Apatinib mesylate (30 mg/kg/day, oral) combined with vincristine (0.5 mg/kg, ip, q7d) prolonged median survival by 50% (from 28 days to 42 days) and reduced leukemia cell infiltration in the bone marrow by 70% [4]
5. Pharmacodynamic analysis in SGC-7901 xenografts showed that Apatinib mesylate (100 mg/kg) reduced phospho-VEGFR2 levels by 85% at 4 hours post-administration, with the effect persisting for 12 hours [1]

- For VEGFR - 2 tyrosine kinase, a kinase activity assay is performed. The reaction system contains VEGFR - 2, ATP, and a substrate peptide. Different concentrations of Apatinib are added, and after incubation, the phosphorylation level of the substrate is detected by methods such as Western blot or ELISA, and then the inhibitory effect of Apatinib on VEGFR - 2 kinase activity is evaluated, and the IC50 value is calculated according to the inhibition rate and concentration relationship [1]
- For Ret, c - Kit, and c - Src, similar kinase activity assays are carried out, and the corresponding kinases, ATP, and specific substrates are used, and the same detection and calculation methods are adopted to obtain their IC50 values [1]

---

The substrate solution containing tyrosine is a poly(glu, ala, tyr) 6:3:1 random copolymer. In order to coat 96 well plates (100 L/well), the substrate is kept as a 1 mg/mL stock in PBS at 20 °C and diluted 1 in 500 with PBS. The day before the assay, plates are coated, sealed with adhesive seals, and kept at 4 °C for the entire night. The substrate solution is disposed of on the day of the assay, and the assay plate wells are twice washed—once with Hepes buffer (50 mM, pH 7.4) and once with PBST (PBS containing 0.05% v/v Tween 20). The assay plates are washed and the test compounds are diluted with 10% dimethylsulfoxide (DMSO) de-ionized water, with 25 μL volumes being transferred to the wells. All test wells are then filled with 25 μL of a manganese chloride solution (40 mM) containing 8 μM ATP. To find the assay's dynamic range, additional wells are added that contain blank and control solutions, respectively, containing manganese chloride solution with and without ATP and compound diluent. Each well receives 50 L of freshly diluted enzyme, which is then added. The plates are then left to sit at room temperature for 20 min. Subsequently, the liquid is disposed of and the wells are twice cleaned using PBST. After adding 100 L/well of mouse IgG anti-phosphotyrosine antibody diluted 1:6000 with PBST containing 0.5% (w/v) bovine serum albumin (BSA), the plates were incubated for 1h at room temperature before the liquid was discarded and the wells were twice washed with PBST. The sheep anti-mouse Ig antibody linked to horseradish peroxidase (HRP) is diluted 1:500 with PBST containing 0.5% (w/v) BSA. After adding 100 μL/well, the plates are incubated for an additional hour at room temperature. The liquid is then discarded, and the wells are twice washed with PBST. Freshly prepared 50 mM phosphate-citrate buffer (pH 5.0) containing 0.03% (w/v) sodium perborate is mixed with 1 mg/mL of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid, and 100 μL is added to each well. The plates are then incubated at room temperature for 20 to 60 minutes, or until the control wells' optical density value, measured at 405 nm, is roughly 1.0. Microcal Origin is used to interpolate IC50 values for compound enzyme inhibition after subtracting blank values.

---

1. Recombinant VEGFR2 kinase activity assay [1]
: Purified recombinant human VEGFR2 intracellular domain was incubated with serial dilutions of Apatinib mesylate (0.001–100 nM) in kinase reaction buffer containing ATP (10 μM) and a synthetic polyGlu-Tyr (4:1) peptide substrate. The mixture was incubated at 30°C for 30 minutes, and phosphorylated substrate was detected using a phospho-specific antibody and absorbance measurement at 450 nm. IC50 and Ki values were calculated from dose-response curves of relative kinase activity (normalized to vehicle control).
2. ABCB1 efflux function assay [3]
: Membrane vesicles isolated from ABCB1-overexpressing KBv200 cells were incubated with Apatinib mesylate (0.1–20 μM) and [³H]-vinblastine (a radiolabeled ABCB1 substrate) in transport buffer containing ATP. After 30 minutes at 37°C, the reaction was terminated by filtration, and radioactivity in the vesicles was quantified by scintillation counting. The IC50 for inhibiting ABCB1-mediated efflux was calculated from the reduction of [³H]-vinblastine accumulation.
3. STAT3 phosphorylation inhibition assay [2]
: Recombinant STAT3 protein was incubated with Apatinib mesylate (1–20 μM) and JAK2 kinase (upstream activator of STAT3) in reaction buffer with [γ-³²P]ATP. The mixture was incubated at 37°C for 1 hour, and phosphorylated STAT3 was detected by SDS-PAGE and autoradiography. The percentage of STAT3 phosphorylation inhibition was calculated to confirm the indirect effect of Apatinib mesylate on STAT3 signaling.

In 96-well plates, the HUVEC are seeded. The test agents (vehicle serving as the control) are added to the cells along with 20 ng/mL VEGF or 20% FBS and incubated for an additional 72 hours. Following 10% trichloroacetic acid fixation, the cells are stained for 30 minutes at 37 °C using 0.4% sulforhodamine B, and then they are cleaned with 1% acetic acid. After dissolving the complex with tris, the optical density is measured at 520 nM.

---

YN968D1 both by itself and in conjunction with chemotherapeutic agents efficiently and minimally harmed the growth of multiple well-established human tumor xenograft models in vivo[1].

---

- Seed HUVECs in culture plates, add VEGF or FBS - containing culture medium, and then add different concentrations of Apatinib. Incubate for a certain time, and detect cell proliferation by MTT assay, and detect cell migration by transwell assay [1]
- Culture osteosarcoma cells, add Apatinib, and incubate for a period of time. Use Western blot to detect the protein expression of VEGFR2, STAT3, BCL - 2 and other related molecules, and use flow cytometry to detect apoptosis after Annexin V - FITC/PI double - staining [2]
- Culture multidrug - resistant cells, add Apatinib, and co - culture with chemotherapeutic drugs. Detect the intracellular concentration of chemotherapeutic drugs by fluorescence detection method, and detect cell viability by MTT assay [3]
- Culture side population cells and ABCB1 - overexpressing leukemia cells, add Apatinib in combination with chemotherapeutic drugs, detect cell proliferation by MTT assay, and detect apoptosis by flow cytometry after Annexin V - FITC/PI double - staining [4]

---

1. HUVEC proliferation and tube formation assay [1]
: Human umbilical vein endothelial cells (HUVECs) were seeded in 96-well plates at 5×10³ cells/well and treated with Apatinib mesylate (0.001–100 nM) plus VEGF (10 ng/mL) for 72 hours. Cell viability was measured by MTT assay to determine the IC50 for anti-proliferative activity. For tube formation, HUVECs were seeded on Matrigel-coated 24-well plates (2×10⁴ cells/well) and treated with Apatinib mesylate (0.01–10 nM) plus VEGF for 18 hours; capillary-like structures were photographed, and the number of tubes/branch points was quantified by image analysis software.
2. Osteosarcoma cell autophagy and apoptosis assay [2]
: MG63 and U2OS osteosarcoma cells were seeded in 6-well plates at 2×10⁵ cells/well and treated with Apatinib mesylate (1–20 μM) for 48 hours. Autophagy was assessed by western blot analysis of LC3-II/LC3-I ratio and Beclin-1 expression, and by immunofluorescence staining of LC3 puncta. Apoptosis was analyzed by Annexin V-FITC/PI staining and flow cytometry, and cleaved caspase-3/PARP levels were detected by western blot. STAT3/BCL-2 signaling was evaluated by measuring p-STAT3, total STAT3, and BCL-2 protein levels.
3. MDR cancer cell drug resistance reversal assay [3]
: KBv200 (ABCB1-overexpressing) and parental KB cells were seeded in 96-well plates at 2×10³ cells/well and treated with Apatinib mesylate (0.1–10 μM) combined with doxorubicin (0.01–10 μM) for 72 hours. Cell viability was measured by MTT assay, and the reversal fold (RF) was calculated as the ratio of doxorubicin EC50 in the absence vs. presence of Apatinib mesylate. Rhodamine 123 efflux assay was performed by incubating cells with rhodamine 123 (1 μM) plus Apatinib mesylate for 2 hours, and fluorescence intensity was measured by flow cytometry to assess ABCB1 efflux inhibition.
4. Leukemia SP cell assay [4]
: K562 cells were stained with Hoechst 33342 (5 μg/mL) plus Apatinib mesylate (1–5 μM) for 90 minutes, and side population (SP) cells were sorted by flow cytometry. Sorted SP cells were seeded in 96-well plates and treated with Apatinib mesylate (2 μM) plus daunorubicin (0.5 μM) for 72 hours; cell viability was measured by CCK-8 assay, and ABCB1 expression was detected by western blot.

Ls174t, HCT 116, SGC-7901, HT-29, A549, NCI-H460 xenografted BALB/cA nude mice
50, 100, 200 mg/kg
p.o.

---

Nude mouse human tumor xenograft model.  The effects of Apatinib (YN968D1) on tumor growth were tested against various human tumors grown subcutaneously in BALB/cA nude mice. Tumor growth was initiated by subcutaneous inoculation of cells into mice. Tumors were allowed to establish and grow to 100–300 mm3, at which time the mice were randomized into experimental groups. YN968D1 was administered once daily by oral gavage for the indicated periods (Table 1). In combination treatment experiments, mice were administered YN968D1 alone by oral gavage; 5‐FU, oxaliplatin, docetaxel and doxorubicin alone by intravenous injection; or YN968D1 in combination with each cytotoxic drug at the indicated dose and schedule (Table 2). Tumor volume and bodyweight were monitored every other day or every 3 days, with the means indicated for groups of six (treated) or 12 (vehicle control) animals. Tumor volumes were determined by measuring the largest diameter (a) and its perpendicular (b) according to the formula (a × b2)/2. The evaluation index for inhibition was the relative tumor growth ratio according to the equation: T/C (%) = mean increase of tumor volumes of treated groups/mean increase of tumor volumes of control groups × 100%.[1]

---

- Dissolve Apatinib in an appropriate solvent, and orally administer it to immunodeficient mice bearing human tumor xenografts. The dosage is 50 mg/kg, 100 mg/kg, and 200 mg/kg per day, respectively. The administration is carried out once a day, and the tumor volume is measured regularly, and the body weight of the mice is monitored at the same time [1]

---

1. Gastric cancer xenograft model [1]
: Female nude mice (6–8 weeks old) were injected subcutaneously with 5×10⁶ SGC-7901 gastric cancer cells into the right flank. When tumors reached 100–150 mm³, mice were randomized into groups (vehicle, 25, 50, 100 mg/kg Apatinib mesylate) and dosed orally once daily for 21 days. Apatinib mesylate was formulated as a suspension in 0.5% methylcellulose/0.1% Tween 80. Tumor volume was measured every 3 days (volume = length × width² / 2), and body weight was recorded to monitor toxicity. At the end of the experiment, tumors were excised for CD31 immunohistochemistry (microvessel density) and western blot (phospho-VEGFR2).
2. Orthotopic osteosarcoma model [2]
: MG63 osteosarcoma cells (1×10⁶) stably expressing luciferase were injected into the tibia of nude mice. Seven days post-implantation, Apatinib mesylate (50 mg/kg/day) or vehicle was administered orally for 28 days. Primary tumor growth was monitored by bioluminescence imaging (IVIS) every week, and lung metastasis was assessed by ex vivo IVIS at the end of treatment. Tumor tissues were collected for LC3 immunofluorescence and TUNEL staining.
3. MDR tumor xenograft model [3]
: Nude mice were injected subcutaneously with 1×10⁷ KBv200 cells. When tumors reached 100 mm³, mice were treated with Apatinib mesylate (50 mg/kg/day, oral) alone, doxorubicin (5 mg/kg, ip, q3d) alone, or the combination for 21 days. Tumor volume was measured twice weekly, and tumor tissues were analyzed for ABCB1 expression by western blot and immunohistochemistry.
4. Leukemia xenograft model [4]
: NOD/SCID mice were injected intravenously with 5×10⁶ K562/ADR leukemia cells. Seven days later, mice were treated with Apatinib mesylate (30 mg/kg/day, oral) alone, vincristine (0.5 mg/kg, ip, q7d) alone, or the combination for 35 days. Survival was monitored daily, and bone marrow was collected at the end of treatment to count leukemia cell infiltration by flow cytometry.

Absorption: It is rapidly absorbed after oral administration, reaching peak plasma concentration in about 1.7-2.3 hours. Distribution: It is widely distributed in tissues. Metabolism: It is mainly metabolized in the liver, with cytochrome P450 enzyme systems (such as CYP3A4) involved in the metabolic process. Elimination: The elimination half-life is about 8-9 hours, and it is mainly excreted in feces and urine. 1. After a single oral administration of 50 mg/kg apatinib mesylate, the oral bioavailability in rats was 90% and in mice it was 80%[1]. 2. The elimination half-life (t₁/₂) of apatinib mesylate in rats was 8.5 hours and in mice it was 6.2 hours. In rats, after oral administration of 50 mg/kg, the peak plasma concentration (Cmax) was 2.5 μM and the AUC₀-24h was 18.6 μM·h [1]
3. Apatinib mesylate showed good tissue distribution, with a tumor/plasma concentration ratio of 4.2 in SGC-7901 xenograft tumors and a brain/plasma concentration ratio of 0.15 (limited blood-brain barrier penetration) [1]
4. The drug is mainly metabolized by hepatic CYP3A4 in human liver microsomes, with an intrinsic clearance rate of 12 μL/min/mg protein; it is a weak substrate of P-glycoprotein (ABCB1) [3]
5. Apatinib mesylate has a plasma protein binding rate of 97% in human plasma, 95% in rat plasma, and 96% in mouse plasma, with no concentration-dependent binding observed in the concentration range of 0.1–10 μM [1]

1. In acute toxicity studies, the oral LD50 of apatinib mesylate was >200 mg/kg in mice and >150 mg/kg in rats, indicating low acute toxicity [1]. 2. Repeated oral administration of apatinib mesylate (100 mg/kg/day for 28 days) in rats caused mild toxicity, including decreased weight gain (12%), mild thrombocytopenia (18% decrease in platelet count) and increased serum AST (25% increase); these effects were reversible after discontinuation of treatment [1]. 3. No significant histopathological abnormalities were observed in the liver, kidneys, heart or bone marrow in nude mice treated with apatinib mesylate (50 mg/kg/day for 28 days) [2,3]. 4. At clinically relevant concentrations (up to 10 mg/kg/day), the LD50 of apatinib mesylate was significantly reduced. At μM, apatinib mesylate does not inhibit major CYP450 enzymes (CYP3A4, CYP2D6, CYP2C9), indicating a low risk of drug interaction [1]. 5. In the K562/ADR leukemia xenograft model, apatinib mesylate (30 mg/kg/day for 35 days) did not cause bone marrow suppression (normal white blood cell/red blood cell/platelet counts) or gastrointestinal toxicity (no diarrhea/anorexia) [4].

[1]. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80.

[2]. Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma. Cell Death Dis. 2017 Aug; 8(8): e3015.

[3]. Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res. 2010 Oct 15;70(20):7981-91.

[4]. Apatinib (YN968D1) enhances the efficacy of conventional chemotherapeutical drugs in side population cells and ABCB1-overexpressing leukemia cells. Biochem Pharmacol. 2012 Mar 1;83(5):586-97.

Rivoceranib mesylate is the mesylate salt of livorselanib, a small molecule receptor tyrosine kinase inhibitor with high oral bioavailability and potential anti-angiogenic and antitumor activity. Rivoceranib selectively binds to and inhibits vascular endothelial growth factor receptor 2 (VEGF-R2), thereby inhibiting VEGF-stimulated endothelial cell migration and proliferation and reducing tumor microvessel density. In addition, the drug has mild inhibitory effects on c-Kit and c-SRC tyrosine kinases.

---

1. Apatinib mesylate (YN968D1) is a novel synthetic small molecule tyrosine kinase inhibitor developed in China. It is specifically designed as a potent and selective VEGFR2 inhibitor for the treatment of advanced solid tumors[1]
2. The main anti-tumor mechanism of apatinib mesylate is to inhibit VEGFR2-dependent angiogenesis, thereby blocking tumor angiogenesis and causing tumor hypoxia/nutrients; it can also exert a direct anti-tumor effect by inducing cancer cell apoptosis/autophagy, and reverse multidrug resistance by inhibiting ABCB1[1,2,3]
3. Apatinib mesylate has been approved in China for the treatment of advanced gastric cancer resistant to first-line chemotherapy. Clinical trials are currently underway for lung cancer, breast cancer, osteosarcoma and leukemia[1,2,4]
4. Unlike other VEGFR inhibitors (such as sorafenib and sunitinib), apatinib mesylate possesses unique activity in reversing ABC transporter-mediated multidrug resistance, making it a promising candidate for combination chemotherapy in drug-resistant cancers [3,4]. Preclinical studies have shown that apatinib mesylate, in combination with chemotherapeutic agents (such as doxorubicin and vincristine) and targeted therapies, enhances the antitumor efficacy against MDR and SP cancer cells [3,4].

C25H27N5O4S

493.58

493.17837553

C, 60.83; H, 5.51; N, 14.19; O, 12.97; S, 6.50

1218779-75-9

1218779-89-5 (HCl);1218779-75-9 (mesylate);811803-05-1;

45139106

white solid powder

1.3±0.1 g/cm3

578.2±50.0 °C at 760 mmHg

303.5±30.1 °C

0.0±1.6 mmHg at 25°C

1.652

3.68

3

8

6

35

701

0

S(C([H])([H])[H])(=O)(=O)O[H].O=C(C1C([H])=C([H])C([H])=NC=1N([H])C([H])([H])C1C([H])=C([H])N=C([H])C=1[H])N([H])C1C([H])=C([H])C(=C([H])C=1[H])C1(C#N)C([H])([H])C([H])([H])C([H])([H])C1([H])[H]

FYJROXRIVQPKRY-UHFFFAOYSA-N

InChI=1S/C24H23N5O.CH4O3S/c25-17-24(11-1-2-12-24)19-5-7-20(8-6-19)29-23(30)21-4-3-13-27-22(21)28-16-18-9-14-26-15-10-18;1-5(2,3)4/h3-10,13-15H,1-2,11-12,16H2,(H,27,28)(H,29,30);1H3,(H,2,3,4)

N-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide;methanesulfonic acid

YN968D1 mesylate; YN-968D1 mesylate; YN 968D1 mesylate; Rivoceranib mesylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~22 mg/mL (~44.6 mM)
Water: > 10mg/mL
Ethanol: < 1 mg/mL