Fig. 1 · Structure

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Navarixin (SCH-527123)

Cat. No. A11555 CAS 473727-83-2

CXCR1/CXCR2 antagonist

SCH527123 is a potent and selective antagonist of the human CXCR1 and CXCR2 receptors with IC50 of 42 nM and 3 nM, respectively.

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Publications for Navarixin

3 publications citing this product

  1. Ruijie Zhang, .et al. , Int J Oncol, 2022, May;60(5):50 PMID: 35315502
  2. Fu S, .et al. , Int J Oncol, 2018, Jul;53(1):349-357 PMID: 29749433
  3. Fu S, .et al. , Anticancer Res, 2018, Nov;38(11):6271-6279 PMID: 30396947

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Biological Activity

Bioactivity / Mechanism

In HPAC pancreatic cancer cells, SCH527123 reduced STAT3 Tyr705 phosphorylation after 24 h at 40–80 μM, while total STAT3 remained broadly unchanged. This is a cellular signaling observation; it does not establish receptor affinity or direct STAT3 inhibition. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
125I-CXCL8-CXCR2 IC50 0.97 nM
Cynomolgus CXCR2 Kd 0.08 nM
Mouse CXCR2 Kd 0.2 nM
Rat CXCR2 Kd 0.2 nM
125I-CXCL8-CXCR1 IC50 43 nM
Cynomolgus CXCR1 Kd 41 nM

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In Vitro Studies

SCH527123 reduced 72-h MTT viability in five pancreatic cancer cell lines. The paper reports cellular IC50 values of 53.49 μmol/l for HPAC and 42.14 μmol/l for BxPC-3. These assay endpoints should be distinguished from receptor-binding potency. [1]

In CAOV3, SKOV3, OVCAR3 and OV75 ovarian cancer cultures, SCH527123 at 15 μM combined with bazedoxifene acetate lowered MTT viability more than either agent alone. SCH527123 monotherapy responses varied, with little reduction in CAOV3 under the plotted condition. The combination result does not establish the effect of SCH527123 alone. [2]

Pancreatic cancer cell viability after SCH527123 exposure

Cell-based study · HPAC, AsPC-1, MIA PaCa-2, BxPC-3 and Capan-1 human pancreatic cancer cells [1]

SCH527123 reduced MTT viability relative to DMSO across the five cell lines. Reported HPAC and BxPC-3 IC50 values describe this 72-h cellular assay.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
MTT viability relative to DMSOqualitative Reduced with increasing SCH527123 concentration; responses vary by cell line[1]
Cellular MTT viabilityIC50 53.49 μmol/l (HPAC); 42.14 μmol/l (BxPC-3)[1]

Literature-Reported Treatment Conditions

Treatment concentration
20, 40, 60, 80 and 100 μM
Exposure duration
72 h
Method
MTT absorbance at 595 nm
Vehicle
DMSO; final percentage not specified
Reported limits
Replicate count and IC50 fit uncertainty are not specified for Figure 1 in the acquired text/caption.
Methods and source locations

Compound reported in the paper: SCH-527123 (Navarixin); Compound label in the paper: SCH527123

Applies to the named material tested in this paper; no validation of a current Adooq lot or salt conversion.

Materials and methods: Cell lines and reagents; MTT cell viability assay; Results: Reparixin and SCH527123 reduce cell viability; Figure 1B

MTT viability relative to DMSO: MTT, 72 h; paper reports mean ± SEM and one-way ANOVA with Tukey post hoc comparisons. — Figure 1B and accompanying Results

Cellular MTT viability: Values transcribed from Results, not estimated from bars. — Results: Reparixin and SCH527123 reduce cell viability; Figure 1B

STAT3 phosphorylation in SCH527123-treated HPAC cells

Cell-based study · HPAC human pancreatic cancer cells [1]

SCH527123 reduced STAT3 Tyr705 phosphorylation without an evident loss of total STAT3 in the displayed blot.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
STAT3 Tyr705 phosphorylation and total STAT3qualitative p-STAT3 decreased; total STAT3 broadly unchanged[1]

Literature-Reported Treatment Conditions

Treatment concentration
40, 60 and 80 μM
Exposure duration
24 h
Method
Western blot
Vehicle
DMSO; final percentage not specified
Reported limits
No densitometric effect size, replicate count or statistical test is supplied for the displayed Figure 5B blot.
Methods and source locations

Compound reported in the paper: SCH-527123 (Navarixin); Compound label in the paper: SCH527123

Applies to the named material tested in this paper; no validation of a current Adooq lot or salt conversion.

Materials and methods: Cell lines and reagents; Western blot analysis; Results: Inhibition of CXCR1/2 signaling pathway reduces activation of downstream effectors; Figure 5B

STAT3 Tyr705 phosphorylation and total STAT3: p-STAT3 Y705 antibody cat. no. 9145; total STAT3 cat. no. 4904; GAPDH loading control. — Figure 5B; accompanying Results; Western blot analysis

Ovarian cell viability with SCH527123 and bazedoxifene

Cell-based study · CAOV3, SKOV3, OVCAR3 and OV75 primary human ovarian cancer cells in culture [2]

The combination lowered MTT viability more than either single agent. SCH527123 monotherapy responses varied; the CAOV3 bar remained close to the DMSO control.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
MTT viability: combination versus either monotherapyqualitative Lower with combination in all four models; CAOV3 SCH527123 monotherapy close to vehicle[2]

Literature-Reported Treatment Conditions

Treatment concentration
SCH527123 15 μM; bazedoxifene acetate 5 μM in CAOV3, SKOV3 and OVCAR3, or 10 μM in OV75
Exposure duration
72 h incubation; Methods also describe overnight treatment before this incubation
Method
MTT absorbance at 595 nm
Vehicle
DMSO control normalized to 100%; final DMSO percentage not specified
Co-treatment
SCH527123 plus bazedoxifene acetate; both monotherapies and DMSO compared
Reported limits
Exact mean viability percentages and raw replicate-level data are not supplied in the acquired text; no bar-height decimals inferred. The description of overnight treatment followed by 72 h is retained without simplifying total exposure.
Methods and source locations

Compound reported in the paper: SCH-527123 (Navarixin); Compound label in the paper: SCH527123

Applies to the named material tested in this paper; no validation of a current Adooq lot or salt conversion.

Materials: SCH and Baze acetate; MTT assay; Statistical analysis; Results: Baze + SCH synergistically inhibit human ovarian cancer cell viability; Figure 3A–D

MTT viability: combination versus either monotherapy: Figure comparisons and qualitative bars directly viewed. General statistics report triplicate experiments, mean ± SEM and one-way ANOVA/Tukey; independence of triplicates is unspecified. — Figure 3A–D; MTT assay; Statistical analysis

In Vivo Studies

In a KM12L4 colon cancer model, oral SCH-527123 reduced liver metastatic burden without significantly changing primary splenic tumor weight. Only the 50 mg/kg group showed a significant reduction in liver-nodule counts in the displayed table. Liver-metastasis incidence remained 90–100%, limiting claims of metastasis prevention. [3]

Liver metastasis and primary tumor growth in a colon cancer model

Animal study · KM12L4 human colon cancer cells implanted in the spleen of female athymic nude mice [3]

SCH-527123 reduced liver metastatic burden and, significantly at 50 mg/kg, liver-nodule counts, while primary splenic tumor weight was unchanged. Liver-metastasis incidence remained 90–100%.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Normalized primary splenic tumor weightqualitative No significant difference between SCH-527123 and vehicle groups[3]
Liver metastatic nodule countMedian (range) Vehicle 22 (17–105); SCH-527123 25 mg/kg: 14 (4–34); 50 mg/kg: 11* (3–26); 100 mg/kg: 16 (0–43)[3]
Normalized liver metastatic burdenqualitative Lower in SCH-527123-treated groups; not a monotonic dose response[3]

Conditions shared by the study groups

Route
Oral gavage
Frequency
Twice daily
Treatment course
3 weeks, starting 24 h after tumor-cell inoculation
Vehicle
20% hydroxypropyl-β-cyclodextrin
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
SCH-527123 25 mg/kg
25 mg/kg body weight per administration
Vehicle gavage; control liver-nodule median 22 (range 17–105), incidence 100%Liver-nodule median 14 (range 4–34); incidence 100%. No significance marker for this nodule count in Figure 1D. Primary splenic tumor weight was not significantly different from vehicle.[3]
SCH-527123 50 mg/kg
50 mg/kg body weight per administration
Vehicle gavage; control liver-nodule median 22 (range 17–105), incidence 100%Liver-nodule median 11 (range 3–26); incidence 90%. Marked significant versus vehicle, p<0.05. Primary splenic tumor weight was not significantly different from vehicle.[3]
SCH-527123 100 mg/kg
100 mg/kg body weight per administration
Vehicle gavage; control liver-nodule median 22 (range 17–105), incidence 100%Liver-nodule median 16 (range 0–43); incidence 90%. No significance marker for this nodule count in Figure 1D. Primary splenic tumor weight was not significantly different from vehicle.[3]
SCH-527123 25 mg/kg
Model: Female athymic nude mice, 6–8 weeks; KM12L4 splenic tumors and liver metastases
Reported limits: Minimum 10 animals per group in Methods; exact group-specific n not stated in Figure 1.
SCH-527123 50 mg/kg
Model: Female athymic nude mice, 6–8 weeks; KM12L4 splenic tumors and liver metastases
Reported limits: Minimum 10 animals per group in Methods; exact group-specific n not stated in Figure 1.
SCH-527123 100 mg/kg
Model: Female athymic nude mice, 6–8 weeks; KM12L4 splenic tumors and liver metastases
Reported limits: Minimum 10 animals per group in Methods; exact group-specific n not stated in Figure 1.
Methods and source locations

Compound reported in the paper: SCH-527123 (Navarixin); Compound label in the paper: SCH-527123

Applies to the named material tested in this paper; no validation of a current Adooq lot or salt conversion.

Methods 2.1–2.2 and 2.7; Results 3.1–3.2; Figure 1A–D

Normalized primary splenic tumor weight: Wet spleen weight normalized using non-tumor-bearing spleens; Figure 1A mean ± SEM. — Results 3.2; Figure 1A

Liver metastatic nodule count: Nodules counted in fixed livers; *p<0.05 versus control, marked only at 50 mg/kg; in-vivo analysis uses Mann–Whitney U. — Figure 1D; Methods 2.2 and 2.7

Normalized liver metastatic burden: Liver wet weight normalized using non-tumor-bearing liver weights; mean ± SEM. No exact percentage adopted because Results range and Figure 1B annotation differ at the upper end. — Results 3.2; Figure 1B

SCH-527123 25 mg/kg · Methods 2.1–2.2 and 2.7; Results 3.1–3.2; Figure 1A–D

SCH-527123 50 mg/kg · Methods 2.1–2.2 and 2.7; Results 3.1–3.2; Figure 1A–D

SCH-527123 100 mg/kg · Methods 2.1–2.2 and 2.7; Results 3.1–3.2; Figure 1A–D

Specifications

Manufacturer Adooq Bioscience
Actions Antagonist
CAS Number 473727-83-2
Applications CXCR1/CXCR2 antagonist
Formula C21H23N3O5
Molecular Weight 397.42
Synonyms SCH 527123
SMILES
CC[C@H](C1=CC=C(O1)C)NC2=C(C(=O)C2=O)NC3=CC=CC(=C3O)C(=O)N(C)C

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 71 mg/mL (178.65 mM)
Water Insoluble
Ethanol 71 mg/mL (178.65 mM)

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Fu S, Chen X, Lin HJ, et al. Inhibition of interleukin 8/C‑X-C chemokine receptor 1,/2 signaling reduces malignant features in human pancreatic cancer cells. International journal of oncology (2018). PMID: 29749433 DOI: 10.3892/ijo.2018.4389 Source material
  2. [2] Zhang R, Roque DM, Reader J, et al. Combined inhibition of IL‑6 and IL‑8 pathways suppresses ovarian cancer cell viability and migration and tumor growth. International journal of oncology (2022). PMID: 35315502 DOI: 10.3892/ijo.2022.5340 Source material
  3. [3] Varney ML, Singh S, Li A, et al. Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. Cancer letters (2011). PMID: 21035946 DOI: 10.1016/j.canlet.2010.10.004 Source material

Publications

3 publications citing this product

  1. Ruijie Zhang, .et al. , Int J Oncol, 2022, May;60(5):50 PMID: 35315502
  2. Fu S, .et al. , Int J Oncol, 2018, Jul;53(1):349-357 PMID: 29749433
  3. Fu S, .et al. , Anticancer Res, 2018, Nov;38(11):6271-6279 PMID: 30396947

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