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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
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Accessible (Haz class 3, 4, 5 or 8), International
Migration inhibitory factor (MIF) is a pleiotropic inflammatory mediator that inhibits macrophage migration in innate and adaptive immunologic responses. 4-IPP is an irreversible MIF inhibitor that binds covalently to MIF to inhibit its activity. It inhibited the viability of bone marrow macrophages (BMMs) with an IC50 value of 104.3µM at 72h. 4-IPP at 5-20µM suppressed the formation of TRAP-positive multinucleated osteoclasts in a dose-dependent manner. 4-IPP treatment at a dose of 20µM also significantly downregulated the expression of genes involved in
BMM precursor fusion (i.e. DC-STAMP), osteoclast maturation (i.e. c-Fos and NFATc1), and bone resorption (i.e. TRAP and CTSK) in BMM-derived osteoclasts. Osteoclasts-treated with 20µM 4-IPP resorbed 3.73±1.24% of the bone discs, whereas the untreated cells resorbed >40% of the total bone area. Incubation of BMMs with 20µM 4-IPP inhibited RANKL-induced NF-κB activation, resulting in the suppression of NFATc1 induction. Treatment with 20µM 4-IPP for 5 days suppressed the formation of TRAP-positive multinucleated osteoclasts in BMMs extracted from wild-type mice but not MIF knockout BMMs. Subcutaneous injection of 4-IPP at a dose of 1 or 5mg/kg every 2 days for 2 weeks reduced the extent of Ti particle-induced bone destruction in mice. Administration of 4-IPP at 1 or 5mg/kg also alleviated the bone loss associated with estrogen deficiency in a mouse model of ovariectomy-induced osteoporosis[1].
4-IPP 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CRC-pc1 and CRC-pc2 organoids
10, 25, 50, 100 µM
24 and 48 hours
Inhibition of the MIF/CD74 signaling axis led to decreased AMPK and AKT phosphorylation, activation of JNK-mediated stress response, resulting in mitochondrial impairment and cell death.
J Exp Clin Cancer Res. 2017 Jan 23;36(1):16.
MM.1S cells
80 µM
24 hours
Enhanced the efficacy of melphalan
J Natl Cancer Inst. 2016 Jul 5;108(11):djw131.
ARP-1 cells
80 µM
24 hours
Downregulated the expression of ITGB5 and ALCAM
J Natl Cancer Inst. 2016 Jul 5;108(11):djw131.
U937 cells
50 µM
72 hours
Evaluated the protective effect of BM cells on AML cells
Cell Death Discov. 2024 Mar 28;10(1):157.
HL-60 cells
50 µM
72 hours
Induced apoptosis in AML cells
Cell Death Discov. 2024 Mar 28;10(1):157.
Astrocytes
100 µM
24 hours
To validate the inhibitory effect of MIF inhibitor 4-IPP on COX2 and mPGES-1 expression in astrocytes. Results showed that 4-IPP significantly reduced the protein levels of COX2 and mPGES-1.
J Neuroinflammation. 2019 Apr 13;16(1):85.
Rat joint capsule fibroblasts
50 µM
24 hours
To validate the inhibitory effect of 4-IPP on MIF-induced TGF-β1 expression, results showed 4-IPP effectively blocked MIF's effect.
Int J Biol Sci. 2021 Apr 29;17(7):1837-1850.
Rat joint capsule fibroblasts
0-2.5 μg/mL
24 hours
To investigate the effect of MIF on TGF-β1 expression, results showed MIF dose-dependently increased TGF-β1 expression.
Int J Biol Sci. 2021 Apr 29;17(7):1837-1850.
RMS cell lines (Rh30, RD, A-204, RMS33-2)
25 µM
24 hours
To evaluate the effect of 4-IPP on RMS cell migration. Results showed that 4-IPP significantly inhibited the migration ability of RMS cells.
Cancer Immunol Immunother. 2016 Dec;65(12):1465-1476.
143B cells
10, 20, 40 µM
24, 48, 96 hours
To evaluate the inhibitory effect of 4-IPP on 143B cell proliferation, results showed 4-IPP significantly inhibited cell proliferation
Clin Transl Med. 2022 Jan;12(1):e652.
HOS cells
10, 20, 40 µM
24, 48, 96 hours
To evaluate the inhibitory effect of 4-IPP on HOS cell proliferation, results showed 4-IPP significantly inhibited cell proliferation
Clin Transl Med. 2022 Jan;12(1):e652.
LOVO
30 µM
48 hours
Inhibition of MIF activity, combined with refametinib significantly reduced STAT3 and MAPK activity, synergistically inhibiting cell proliferation
Mol Oncol. 2018 Aug;12(8):1398-1409.
HCT116
30 µM
48 hours
Inhibition of MIF activity, combined with refametinib significantly reduced STAT3 and MAPK activity, synergistically inhibiting cell proliferation
Mol Oncol. 2018 Aug;12(8):1398-1409.
HTB-5 cells
30-50 µM
48-72 hours
Evaluate the inhibitory effect of 4-IPP on bladder cancer cell proliferation, results showed 4-IPP is more effective than ISO-1
J Pathol. 2023 Jan;259(1):46-55.
HTB-9 cells
30-50 µM
48-72 hours
Evaluate the inhibitory effect of 4-IPP on bladder cancer cell proliferation, results showed 4-IPP is more effective than ISO-1
J Pathol. 2023 Jan;259(1):46-55.
PBMCs
50 µM
5 days
To investigate the effect of 4-IPP on T cell proliferation. Results showed that high concentrations of 4-IPP inhibited T cell proliferation.
Cancer Immunol Immunother. 2016 Dec;65(12):1465-1476.
HSJD-NB01
5 µM
72 hours
Evaluate the effect of 4-IPP on the viability of HSJD-NB01 cells, results showed that 4-IPP significantly reduced the viability of HSJD-NB01 cells
BMC Cancer. 2022 Jun 17;22(1):669.
IMR5
5 µM
72 hours
Evaluate the effect of 4-IPP on the viability of IMR5 cells, results showed that 4-IPP significantly reduced the viability of IMR5 cells
BMC Cancer. 2022 Jun 17;22(1):669.
SH-SY5Y
5 µM
72 hours
Evaluate the effect of 4-IPP on the viability of SH-SY5Y cells, results showed that 4-IPP significantly reduced the viability of SH-SY5Y cells
BMC Cancer. 2022 Jun 17;22(1):669.
LAN-1
5 µM
72 hours
Evaluate the effect of 4-IPP on the viability of LAN-1 cells, results showed that 4-IPP significantly reduced the viability of LAN-1 cells
BMC Cancer. 2022 Jun 17;22(1):669.
4-IPP 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
SCID mice
Human MM xenograft model
Intraperitoneal injection
0.5 mg/mouse
Every 3 days for 15 days
4-IPP alone had no therapeutic effect in vivo, but significantly enhanced the effectiveness of melphalan and prolonged mouse survival
J Natl Cancer Inst. 2016 Jul 5;108(11):djw131.
Mice
Nippostrongylus brasiliensis infection model
Intraperitoneal injection
1 mg
Administered every other day during infection
Inhibition of MIF activity resulted in weakened intestinal epithelial responses, including reduced tuft cell hyperplasia and RELM β expression
Mucosal Immunol. 2022 Jun;15(6):1243-1256
Mice
Nippostrongylus brasiliensis infection model
Intraperitoneal injection
1 mg
Every other day during infection
Inhibition of MIF activity resulted in defective intestinal immune responses, including lack of intestinal epithelial tuft cell hyperplasia or upregulation of goblet cell RELM β
Mucosal Immunol. 2022 Jun;15(6):1243-1256
Mice
Heligmosomoides polygyrus infection model
Intraperitoneal injection
1 mg
Every other day, during infection
4-IPP significantly compromised anti-parasite immunity in wild-type mice, showing increased adult worm burdens and egg output.
Front Immunol. 2019 Oct 24;10:2375
Sprague Dawley rats
Post-traumatic joint contracture model
Intra-articular injection
10 μL of 100 mM
Single injection
To study the effect of 4-IPP on joint capsule inflammation and fibrosis, results showed 4-IPP significantly reduced TGF-β1 expression and inflammatory response.
Int J Biol Sci. 2021 Apr 29;17(7):1837-1850.
Male SD rats
Ovalbumin (OVA)-induced asthma model
Intraperitoneal injection
5 mg/kg
Three times a week for 8 weeks
4-IPP treatment significantly reduced the concentrations of Th2-type cytokines IL-5 and IL-13 in lung tissues, attenuated airway resistance, and suppressed bronchial wall thickening, epithelial goblet cell hyperplasia, subepithelial collagen fiber deposition, and bronchial muscularization.
Respir Res. 2023 Sep 6;24(1):216
Nude mice
HOS-derived xenograft model
Intraperitoneal injection
5, 20 mg/kg
Every other day for 3 weeks
To evaluate the inhibitory effect of 4-IPP on tumor growth in vivo, results showed 4-IPP significantly inhibited tumor growth and metastasis
Clin Transl Med. 2022 Jan;12(1):e652.
Sprague-Dawley rats
Spinal cord contusion model
Injection at lesion sites
8 μl of 100 mM
Single injection
To evaluate the inhibitory effect of 4-IPP on COX2 and mPGES-1 expression after spinal cord injury. Results showed that 4-IPP significantly reduced the protein levels of COX2 and mPGES-1 and decreased PGE2 production.
J Neuroinflammation. 2019 Apr 13;16(1):85.
Sprague-Dawley rats
Spinal cord contusion model
Injection at the lesion site
8 μl of 100 mM
Single injection
To evaluate the effect of 4-IPP on CCL5 expression post-SCI, results showed 4-IPP significantly reduced CCL5 protein levels
J Neuroinflammation. 2018 Sep 4;15(1):253
NSG mice
U937.GFP-FFLuc cells systemic engraftment model
Intraperitoneal injection
80 mg/kg
Every other day until the end of the experiment (days 19-23)
Evaluated the effect of 4-IPP on leukemia burden and tumor microenvironment
Cell Death Discov. 2024 Mar 28;10(1):157.
Mice
BBN-induced bladder cancer model
Intraperitoneal injection
80 mg/kg
Once daily for 4 weeks
Evaluate the inhibitory effect of 4-IPP on bladder cancer tumor formation, results showed 4-IPP reduced bladder weights and tumor stage
J Pathol. 2023 Jan;259(1):46-55.
Nude mice
Neuroblastoma xenograft model
Intraperitoneal injection
80 mg/kg
3 days a week every 2 days for 4 weeks
Evaluate the effect of 4-IPP on tumor growth in neuroblastoma xenograft model, results showed that 4-IPP significantly delayed tumor growth and improved survival
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