PhIP affects miRNA expression in a wide range of ways that mostly overlap. PhIP activates the estrogen receptor alpha (ERα) to produce effects that are widely distributed. One significant non-DNA damaging oncogenic pathway in breast cancer may be PhIP-induced dysregulation of miRNA [2].

PhIP forms DNA adducts in the prostate and induces oxidative stress, acinar atrophy, and prostatic inflammation in rodents [1]. In hCYP1A mice, PhIP induced inflammation, epithelial cell damage, and prostatic intraepithelial neoplasia in the dorsolateral prostate lobe compared with the ventral lobe.

Absorption, Distribution and Excretion
Fischer 344 rats were administered a single dose of 0.60 mg/rat (2-14)C-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) via gavage. Radioactivity in feces, urine, blood, serum proteins, hemoglobin, and tissues was measured at 12, 24, 48, and 96 hours post-administration. One major radioactive component and four minor radioactive components were found in urine, and one major radioactive component and two minor radioactive components were found in feces. Feces were the primary route of excretion, accounting for 78% of the total dose within the first 24 hours post-administration, and unmetabolized PhIP accounted for 51% of the total dose in feces. Unmetabolized PhIP was also confirmed to be the major radioactive component in the bile and feces of animals that received a single dose via intraperitoneal injection. Only a small dose was present in the blood, and the main persistent binding form of PhIP in the blood was bound to hemoglobin. Twelve hours after administration, the highest radioactivity concentrations were observed in the colon and cecum, followed by the kidneys and liver. At 24 hours post-administration, 80-90% of the radioactive material in the tissues was insoluble in ethanol, indicating covalent binding to macromolecules.
...Utilizing the high sensitivity of accelerator mass spectrometry, the bioavailability and metabolic pathways of PhIP at human dietary doses were investigated. (2-14) C-PhIP was administered to male C57BL/6 mice via gavage (41 ng/kg). Tissue and excrement were collected over the following 96 hours. Throughout the study, 100% of the administered dose was excreted in urine (90%) and feces (10%). Radiocarbon-labeled PhIP was rapidly absorbed from the gastrointestinal tract, with peak radiocarbon levels in whole blood and urine reaching 1 hour post-exposure. Fecal ¹⁴C levels peaked at 12 hours. Radiocarbon levels in tissues peaked at 3 hours, with the highest concentrations observed in the intestines, stomach, and liver, followed by the kidneys, pancreas, lungs, and spleen. Low concentrations of PhIP-derived ¹⁴C (0.01-0.04% of the administered dose) were detectable in tissues 48-96 hours post-exposure, likely due to covalent binding to proteins or DNA. At this dose, the calculated half-life of PhIP was 1.14 hours. …The transfer of PhIP to fetuses and newborns following a single intraperitoneal injection (4.7-5.2 mg/kg body weight) of PhIP in pregnant or lactating C57Bl/6 mice was investigated by tissue extraction and high-performance liquid chromatography. The results showed that unaltered (3)H-PhIP could be transferred to the fetus via the placenta; the highest PhIP levels were observed in the fetus during late pregnancy. In late pregnancy, autoradiography analysis of mice intravenously injected with (2-14)C-PhIP (1.4 mg/kg) showed highly and selectively localized radioactivity to the pigmentary region of the fetal eye, with moderate levels of radioactivity observed in the fetal liver, gastrointestinal contents, urine, and uterine fluid. High-performance liquid chromatography (HPLC) analysis of newborn mice exposed to intraperitoneal injection of (3)H-PhIP (5.2 mg/kg) from lactating mothers for 4 hours showed the presence of unchanged PhIP, indicating that PhIP is excreted in the mother's milk. These results suggest that exposure to PhIP during pregnancy and lactation may lead to the transfer of this food mutagen to the fetus and infant. High-temperature cooking of meat, fish, or poultry produces heterocyclic aromatic amines (HAAs), which may be metabolically activated into mutagenic or carcinogenic intermediates. Cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) are primarily involved in this type of biotransformation… This study determined the relationship between the activities of these two enzymes and the urinary excretion of unmetabolized products and phase II conjugates of two heterocyclic amines (HAAs): MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). Subjects consumed meat containing known amounts of MeIQx and PhIP, and urine was collected 0–12 hours and 12–24 hours postprandial. The urine was acid-treated to determine the levels of MeIQx and PhIP, which quantitatively hydrolyzes the phase II conjugates to their respective parent amines. Extracts containing HAAs were purified by immunoaffinity chromatography and analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry. Following acid hydrolysis, the concentration of MeQx in urine increased 3-21 times within 0-12 hours. After acid treatment, the total amount of MeQx excreted in urine within 0-12 hours (unmetabolites and their N2-glucuronide and sulfamate metabolites) was 10.5 ± 3.5% (mean ± standard deviation) of the administered dose, while the total amount of PhIP excreted within 0-12 hours (unmetabolites and their acid-labile conjugates) was 4.3 ± 1.7% (mean ± standard deviation) of the administered dose. After acid treatment, the total amount of PhIP excreted in urine within 12-24 hours was 0.9 ± 0.4% (mean ± standard deviation) of the administered dose. Linear regression analysis of the excretion of MeQx and PhIP (expressed as a percentage of the ingested dose) in all subjects within 0-12 hours showed a low but significant correlation between the two (r = 0.37, P = 0.005). Linear regression analysis showed that lower levels of total urinary MeIQx (unmetabolites plus N2-glucuronide and sulfamate metabolites) were associated with higher CYP1A2 activity, while total urinary PhIP (unmetabolites plus conjugates) was not correlated with CYP1A2 activity. These results suggest that in humans, the metabolism and distribution of MeIQx are more influenced by CYP1A2 activity than PhIP. Linear regression analysis did not find an association between NAT2 activity and urinary excretion levels of either MeIQx or PhIP (unmetabolites plus acid-labile conjugates). More complete data on the absorption, distribution, and excretion of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (7 compounds) can be found on the HSDB record page. Metabolism/Metabolites This study aimed to assess the effects of cruciferous vegetable intake on PhIP metabolism in 20 non-smoking white male subjects. The study was divided into three 12-day phases: two phases of avoiding cruciferous vegetables (Phase 1 and Phase 3) and one phase of a high-cruciferous-vegetable diet (Phase 2), in which subjects consumed 250 g of Brussels sprouts and 250 g of broccoli daily. At the end of each study phase, subjects consumed a cooked meat meal containing 4.90 micrograms of PhIP and urine samples were collected for up to 48 hours. The intake of cruciferous vegetables significantly increased the activity of hepatic CYP1A2, which was confirmed by changes in salivary caffeine kinetics. …In Phases 1 and 3, the excretion of N(2)-hydroxy-N(2)-PhIP-glucuronide in 0–48 hour urine samples was six times that of N(2)-hydroxy-PhIP-N(3)-glucuronide. Intake of cruciferous vegetables significantly increased the excretion of N(2)-hydroxy-PhIP-N(2)-glucuronide in urinary samples from 0 to 48 hours, reaching 127% and 136% of the levels observed in Phase 1 and Phase 3, respectively. In contrast, the urinary excretion of N(2)-hydroxy-PhIP-N(3)-glucuronide remained unchanged. In Phase 1 and Phase 3, the urinary excretion of the two PhIP metabolites accounted for approximately 39% of the PhIP dose, while in Phase 2, this proportion was approximately 49%. This study demonstrates that intake of cruciferous vegetables can induce Phase I and Phase II metabolism of PhIP in humans. Male Fischer 344 rats were given a single injection of 0.03–30 mg/kg of (2–14)C-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ((14C)PhIP), and the radioactivity in urine and feces was measured within 48 hours. Major metabolites were identified and quantified. The dose had little effect on the composition of metabolites in urine, but it did affect the composition of metabolites in feces. PhIP was metabolized more efficiently at higher doses. In addition, rats were pretreated with Aroclor 1254 (PCB), 3-methylcholanthrene (MC), phenobarbital (PB), PhIP, and corn oil, respectively, before a single administration of (14)C-PhIP, and compared with a control group that received (14)C-PhIP only. Major metabolites in urine and feces of each group were quantified, and the binding of PhIP to serum proteins, hemoglobin, and specific tissues was determined. Pretreatment with MC and PCB resulted in increased 4'-hydroxylation of PhIP in urine and decreased N-hydroxylated metabolites. Pretreatment with PB resulted in increased N-hydroxylated metabolites but decreased 4'-hydroxylation. Both MC and PCB pretreatment resulted in increased binding of PhIP to the liver and kidneys, but decreased binding to other tissues. Animals pretreated with PhIP showed no significant difference compared to untreated groups; however, PB pretreatment generally resulted in decreased PhIP binding in tissues.
...Loss of function of the adenomatous polyposis (APC) gene product is an early and common event in the development of colorectal cancer in humans. Normal (Apc(+/+)) and precancerous (Apc(Min/+)) colonic epithelial cells of mice (where Min represents multiple intestinal tumors) can be used to study the promotion of carcinogenesis...The metabolism of (14) C-PhIP in these two mouse cell lines was investigated. Cells induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) metabolized PhIP to 4'-OH-PhIP, the major metabolite for PhIP detoxification. Furthermore, 5-OH-PhIP was identified, indicating the formation of an intermediate active metabolite, which is produced by the degradation of N-acetoxy-PhIP conjugates. These metabolites were produced significantly higher in Apc(Min/+) cells than in other cell types. Demethylated metabolites were also observed, indicating significant CYP1 family-dependent metabolic activity in the colon. Small amounts of hydroxyglucuronide-PhIP metabolites were observed in Apc(Min/+) cells, while glucuronidation is an important step in the detoxification pathway. Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) experiments showed that TCDD induction significantly affected the gene expression of CYP1A1, CYP1A2, and CYP1B1 in Apc(Min/+) cells. N-acetyltransferase-2 expression levels were also higher in these cells. Therefore, the stronger the bioactivation capacity of PhIP metabolism measured in Apc(Min/+) cells, the higher the probability of generating new in situ mutations. The metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was studied in mice. In 3-methylcholanthrene-induced mice, intraperitoneal injection of 0.1, 1.0, and 10 mg/kg (¹⁴C) PhIP resulted in urinary and fecal excretion of 16% and 42-56% of the administered dose, respectively, within 24 hours. Urinary excretion of the unchanged parent compound was only 0.5-0.8% of the administered dose. At all doses, the major urinary metabolite was identified as 4'-(2-amino-1-methylimidazo[4,5-b]pyridin-6-yl)phenyl sulfate, which accounted for approximately 5% of the dose. More than 13% of the 10 mg/kg dose in the urine of uninduced mice was excreted as sulfate conjugates. The excretion of 2-amino-1-methyl-6-(4'-hydroxy)phenylimidazo[4,5-b]pyridine (4'-hydroxy-PhIP) and its glucuronide conjugate (N-hydroxy-PhIP) in the urine of uninduced mice was also higher than that in induced mice (4-fold). The urinary excretion of P450-derived metabolites decreased after induction, in contrast to the increased metabolite production in liver microsomal formulations. At a concentration of 50 μM (3)H-PhIP, the amounts of 4'-hydroxy-PhIP and N-hydroxy-PhIP produced by inducing microsomes were nearly 7-fold and 3-fold higher, respectively, than those produced by uninduced microsomes. At concentrations below 10 μM, the microsomes prepared by induction almost completely converted PhIP into an unknown metabolite not retained by the C18 column. This metabolite is also produced upon incubation with 4'-hydroxy-PhIP or N-hydroxy-PhIP, but the rate of production in uninduced animal microsomes is much slower. (3) The covalent binding of H-PhIP to microsomal proteins is concentration-dependent and 2 to 4 times higher in induced microsomes than in uninduced microsomes. In the liver and kidneys of mice induced with (14)C-PhIP, the covalent binding of (14)H-PhIP to microsomal proteins is dose-dependent. At a dose of 10 mg/kg PhIP, the level of adduct produced in the liver of induced mice was 1.7 times higher than in uninduced mice, but the binding rate was higher in the kidneys of uninduced animals. These studies suggest that cytochrome P450 and other exogenous enzymes play important roles in the metabolism, distribution, and activation of PhIP. For more complete metabolite/metabolite data on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (28 metabolites in total), please visit the HSDB record page. Known human metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine include N2-glucuronide of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

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Biological half-life
... (2-14)C-PhIP was administered to C57BL/6 male mice by gavage (41 ng/kg). Tissue and excretory samples were collected over the following 96 hours… The half-life of PhIP at this dose was calculated to be 1.14 hours.

Interactions
To investigate the mechanism by which the citrus flavonoid naringin inhibits the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, the most abundant mutagenic heterocyclic amine in food), we conducted a chemical model reaction. GC-MS analysis showed that naringin dose-dependently reduced the level of phenylacetaldehyde, a key intermediate in the PhIP formation pathway. Subsequently, LC-MS analysis of various model systems containing PhIP precursors such as phenylalanine, glucose, and creatinine revealed that naringin scavenges phenylacetaldehyde through adduct formation. Isotope labeling studies indicated that the hypothesized adduct contained a fragment derived from phenylalanine. The direct reaction of phenylacetaldehyde with naringin further confirmed that naringin can form adducts with phenylacetaldehyde, thereby reducing the activity of phenylacetaldehyde in PhIP formation. Two of these adducts were subsequently isolated and purified. One-dimensional and two-dimensional nuclear magnetic resonance spectroscopy analysis determined their structures to be 8-C-(E-phenylvinyl)naringin (1) and 6-C-(E-phenylvinyl)naringin (2), respectively, indicating that C-6 and C-8 are the two active sites for naringin adduct formation. These two adducts were also found in a heat-processed beef model, suggesting that phenylacetaldehyde capture is a key mechanism by which naringin inhibits PhIP formation. The effects of combined treatment with sodium nitrite (NaNO₂) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) on mammary tumor induction in female Sprague-Dawley (SD) rats were evaluated. Six-week-old animals were administered 100 mg/kg body weight of PhIP twice weekly by gavage for 4 weeks, during which 0 or 0.2% NaNO₂ was added to their drinking water. Control group rats received only 0.2% NaNO₂ treatment for 4 weeks, or drank water without any added substances throughout the 48-week experiment, and were not treated with carcinogens. The first tumor appeared significantly later in the PhIP+NaNO₂ group than in the PhIP-only group. During the experiment, the incidence, number, and volume of mammary tumors in this group showed a decreasing trend, although there were no statistically significant differences between groups at the final sacrifice. These results indicate that NaNO₂ does not enhance PhIP-induced mammary cancer in rats, but rather has a certain inhibitory effect. Five-week-old male F344 rats were irradiated with X-rays, and 16 weeks after the first irradiation, they were administered 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) via intragastric instillation. Among the 25 animals treated with X-rays + PhIP, 4 showed pyloric tumors in the proventriculus at 12 months after administration. No such lesions were found in the chemical group or the X-ray-only group. Intestinal metaplasia and some tumor-inducing CDX2 were positive. This suggests that the presence of intestinal metaplasia may increase the sensitivity of colonic carcinogens to gastric tumors. This study aimed to investigate whether the previously observed phenomenon of quercetin increasing PhIP transport through Caco-2 monolayer cells could be confirmed in an in vivo rat model. Simultaneous administration of 1.45 μmol PhIP/kg body weight and 30 μmol quercetin/kg body weight significantly increased the AUC (0–8 hr) of PhIP in rat blood, reaching 131 ± 14% of the AUC (0–8 hr) of the PhIP-only group. Significant increases in blood PhIP levels were detected at 15, 30, 45, and 180 minutes post-administration. At 4 and 8 hours post-administration, the difference in blood PhIP levels between the two groups disappeared. In vitro and computer simulations of PhIP transport were performed using Caco-2 cells and the previously described PhIP transport kinetic model, showing that the relative increase in PhIP transport induced by quercetin depends on the concentrations of both compounds. Substituting the PhIP and quercetin concentrations used in in vivo experiments into the kinetic model, the predicted effect of quercetin on PhIP transport was consistent with the actual effect observed in vivo at 131%. This leads to the conclusion that quercetin can enhance the bioavailability of the procarcinogen PhIP in rats, suggesting that this previously considered beneficial food ingredient may have potential adverse effects. For more complete data on interactions of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (a total of 20 compounds), please visit the HSDB record page.

[1]. Metabolic Activation of the Cooked Meat Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine in Human Prostate. Toxicol Sci. 2018 Jun 1;163(2):543-556.

[2]. Papaioannou MD, et ak. The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) elicits estrogenic-like microRNA responses in breast cancer cells. Toxicol Lett. 2014 Aug 17;229(1):9-16.

According to data from the International Agency for Research on Cancer (IARC) of the World Health Organization, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is carcinogenic. PhIP is an imidazopyridine compound with the structure 1H-imidazo[4,5-b]pyridine, where the 1, 2, and 6 positions are substituted with methyl, amino, and phenyl groups, respectively. It is one of the most abundant mutagenic heterocyclic amines found in cooked meat and fish, exhibiting both carcinogenic and mutagenic properties. It is an imidazopyridine compound and also a primary amine compound. PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) has been used in clinical trials for basic scientific research on pancreatic cancer. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a synthetic, off-white crystalline solid, soluble in dimethyl sulfoxide and methanol. It is produced in small quantities for research purposes. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is naturally produced during the cooking of muscle-based foods (meat and fish). The amount of this chemical produced depends on the cooking temperature, cooking time, and cooking method (direct or indirect cooking). It is one of the most abundant heterocyclic amines in a typical Western diet. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine has also been detected in processed food flavorings, beer, wine, and cigarette smoke. It is likely a human carcinogen. (NCI05)
1-Methyl-6-phenyl-1H-imidazo[4,5-b]pyridine-2-amine is a food-associated mutagen and has been reported to be the most abundant heterocyclic amine in cooked meat and fish.
See also: Beef (partial); Cooked chicken (partial); Cooked eel (partial)... See more...

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Mechanism of Action
Heterocyclic amines (HCAs) are a class of mutagenic/carcinogenic compounds produced during the pyrolysis of creatine, amino acids, and proteins. The main heterocyclic amine subclasses found in the human diet include aminoimidazo[4,5-f]aromatics (AIAs), such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Except for DiMeIQx, all the other compounds have been shown to be carcinogenic in animals… It is currently known that metabolic activation leading to the formation of DNA adducts is key to the mutagenicity and carcinogenicity of these compounds. All the AIAs studied can form adducts with guanine bases, with the main adduct forming at the C8 position. Two AIAs, IQ and MeIQx, can also form small adducts at the N2 position of guanine. A growing body of literature reports the mutational profile induced by AIA-guanine adducts. Studies of AIA-induced animal tumors have begun to link AIA-DNA adduct-induced mutational events to mutations in key genes related to tumorigenesis…
PhIP possesses potent estrogenic activity, inducing transcription of estrogen (E2)-regulated genes, E2-dependent cell proliferation, progesterone receptor upregulation, and activation of the mitogen-activated protein kinase signaling pathway… This report… shows that… doses as low as 10⁻¹¹ mol/L of PhIP can have a direct effect on a rat pituitary lactogenic cell model (GH3 cells), inducing cell proliferation and prolactin synthesis and secretion. PhIP-induced pituitary cell proliferation and prolactin synthesis and secretion can be attenuated by estrogen receptor (ER) inhibitors, indicating that the effect of PhIP on lactogenic cell responses is mediated by ERα. Given the close association between estrogen, progesterone, prolactin, and breast cancer, PhIP's hormone-like activity further supports the tissue-specific carcinogenicity of this chemical from a mechanistic perspective. Furthermore, recent epidemiological studies have reported an association between consuming cooked red meat and breast cancer in premenopausal and postmenopausal women, consistent with the above observations. ...In addition to its genotoxicity, recent studies have shown that PhIP can activate estrogen receptor-mediated signaling pathways at doses similar to those present in the body after consuming cooked meat...This study...investigates whether such doses of PhIP can affect estrogen receptor-independent signal transduction via the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) pathway, thereby influencing the proliferation and migration of human breast epithelial cell line MCF10A and prostate cancer cell line PC-3. At proliferative doses (10⁻¹¹ to 10⁻⁷ mol/L) of PhIP, the phosphorylation levels of MAPK/ERK kinases 1/2 and ERK rapidly and transiently increased. Inhibition of this pathway significantly reduced PhIP-induced MCF10A cell proliferation and PC-3 cell migration. The data in this study demonstrate that PhIP, at levels close to human dietary exposure, stimulates cell signaling pathways leading to increased cell growth and migration, processes closely associated with tumorigenesis and development. These findings strongly support the role of PhIP as a tumor initiator and promoter, suggesting that dietary exposure to this compound may contribute to the development of human cancers. The β-catenin/T cytokine (Tcf) signaling pathway is persistently activated in most human colorectal cancers, accompanied by altered Bcl-2 expression. Similarly, in rats, both β-catenin and Bcl-2 expression were elevated in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colon tumors. To investigate whether β-catenin/Tcf directly regulates rat Bcl-2 transcription, the authors cloned and identified the corresponding promoter region, finding it to have 70.1% sequence similarity to human BCL2. Both LiCl and exogenous β-catenin (including oncogenic mutants of β-catenin found in PhIP-induced colon tumors) enhanced Bcl-2 promoter activity. Protein/DNA microarray analysis showed that E2F1, rather than β-catenin/Tcf, interacted most strongly with the rat Bcl-2 promoter. Exogenous E2F1 enhanced rat Bcl-2 promoter activity, except for mutants with E2F1 deletion sites. As expected, β-catenin induced the expression of its downstream target c-Myc, as well as E2F1 and Bcl-2, while siRNAs targeting c-Myc or E2F1 blocked this process. These findings suggest that Bcl-2 overexpression in PhIP-induced colon tumors may be achieved through an indirect pathway involving β-catenin, c-Myc, and E2F1. For more complete data on the mechanisms of action of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridines (7 in total), please visit the HSDB record page.

224.106

105650-23-5

1530

White to light yellow solid powder

1.3 g/cm3

468.9ºC at 760 mmHg

300ºC

237.4ºC

5.74E-09mmHg at 25°C

1.699

2.798

1

3

1

17

264

0

CN1C2=C(N=CC(=C2)C3=CC=CC=C3)NC1=N

UQVKZNNCIHJZLS-UHFFFAOYSA-N

InChI=1S/C13H12N4/c1-17-11-7-10(9-5-3-2-4-6-9)8-15-12(11)16-13(17)14/h2-8H,1H3,(H2,14,15,16)

1-methyl-6-phenylimidazo[4,5-b]pyridin-2-amine

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 : ~25 mg/mL (~111.48 mM)

Solubility in Formulation 1: ≥ 0.56 mg/mL (2.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 5.6 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.

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Solubility in Formulation 2: ≥ 0.56 mg/mL (2.50 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 5.6 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)