NPASS Compound

Natural Product: NPC118787

Natural Product ID	NPC118787
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Pinnatifidanin B Ix
IUPAC Name	4-[(1R,2R)-3-hydroxy-1-methoxy-2-[2-methoxy-4-[(E)-3-methoxyprop-1-enyl]phenoxy]propyl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2430310
PubChem CID	72189216
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0000190] Methoxyphenols

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 57 58 0 0 0 0 0 0 0 0999 V2000 -7.5298 -1.6476 -2.0759 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9637 -1.0946 -0.8950 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4866 0.1955 -0.6919 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9888 0.2098 -0.6474 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3148 0.6234 0.3981 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8658 0.6603 0.4994 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2925 1.1391 1.6693 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9276 1.1884 1.8067 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0742 0.7582 0.7740 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6565 0.2751 -0.4065 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0129 0.2463 -0.4948 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8133 -0.1576 -1.4454 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4574 -0.6338 -2.6115 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2006 0.8059 0.9054 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4645 0.9039 1.1563 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1868 -0.4423 1.0916 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6402 -0.2885 1.1694 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3003 -0.1343 2.3658 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6547 0.0132 2.4446 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3964 0.0090 1.2928 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7848 -0.1438 0.0468 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4177 -0.2895 0.0104 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5694 -0.1416 -1.0805 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1389 -0.2792 -2.3956 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7847 0.1552 1.3059 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6515 -1.3070 2.0167 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9981 -2.3928 1.4918 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2907 1.8124 0.2287 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8061 3.1138 0.2780 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9771 -2.6768 -2.1286 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8735 -1.1136 -2.9791 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4337 -1.8034 -2.1441 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9259 0.6380 0.2010 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8479 0.7801 -1.5901 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4606 -0.1321 -1.5072 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9196 0.9592 1.2430 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9057 1.4797 2.4883 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4468 1.5626 2.7211 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4603 -0.1263 -1.4087 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1656 0.1721 -2.9641 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1043 -1.4892 -2.3213 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7492 -0.8979 -3.4093 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6439 1.3601 2.1855 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9391 -0.8641 0.0847 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7219 -0.1318 3.2582 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1447 0.1330 3.3974 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9175 -0.4116 -0.9573 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1161 0.0891 -2.5014 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8064 0.3563 -3.0326 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2641 -1.3564 -2.6920 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3982 -0.3154 0.6756 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1366 -2.1502 0.8394 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5753 -2.9640 2.3481 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7134 -3.1151 0.9992 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3620 1.4074 -0.7835 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3118 1.8311 0.6636 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3178 3.2946 1.1068 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 9 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 20 25 1 0 16 26 1 0 26 27 1 0 15 28 1 0 28 29 1 0 11 6 1 0 22 17 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 5 36 1 0 7 37 1 0 8 38 1 0 11 39 1 0 13 40 1 0 13 41 1 0 13 42 1 0 15 43 1 1 16 44 1 6 18 45 1 0 19 46 1 0 22 47 1 0 24 48 1 0 24 49 1 0 24 50 1 0 25 51 1 0 27 52 1 0 27 53 1 0 27 54 1 0 28 55 1 0 28 56 1 0 29 57 1 0 M END

Standard InCHIKey	RZLBDMQWYCAIEA-QDWIBDRMSA-N
Standard InCHI	InChI=1S/C22H28O7/c1-25-11-5-6-15-7-10-18(20(12-15)27-3)29-21(14-23)22(28-4)16-8-9-17(24)19(13-16)26-2/h5-10,12-13,21-24H,11,14H2,1-4H3/b6-5+/t21-,22-/m1/s1
SMILES	COC/C=C/c1ccc(c(c1)OC)O[C@@H]([C@@H](c1ccc(c(c1)OC)O)OC)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	404.18	Volume:	415.032 ? Van der Waals volume.
Dense:	0.974	LogP:	1.715 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.064 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.855 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	13.0
TPSA:	86.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.595	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.361	Fsp³:	0.364
MCE-18:	28.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.247	Fluc inhibitor:	0.701 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.179 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.543 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.448	Promiscuous compounds:	0.384

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.106	MDCK Permeability:	-4.868
Pgp-inhibitor:	0.688	Pgp-substrate:	0.082
PAMPA:	0.198 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.188
20% Bioavailability (F20%):	0.635	30% Bioavailability (F30%):	0.478
50% Bioavailability (F50%):	0.944

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.146
Plasma Protein Binding (PPB):	88.173%	Volume Distribution (VD):	0.026
Fu:	10.779% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.745
BSEP inhibitor:	0.955

ADMET: Metabolism

CYP1A2-inhibitor:	0.798	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.719	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.839	CYP2C9-substrate:	0.005
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.512
CYP3A4-inhibitor:	0.776	CYP3A4-substrate:	0.562
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.808
HLM stability:	0.027 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

8.376

Half-life (T1/2):

1.236

ADMET: Toxicity

hERG Blockers:	0.15	hERG Blockers (10um):	0.174
Human Hepatotoxicity (H-HT):	0.751	Drug-induced Liver Injury (DILI):	0.498
AMES Toxicity:	0.884	Rat Oral Acute Toxicity:	0.118
Maximum Recommended Daily Dose:	0.106	Skin Sensitization:	0.995
Carcinogencity:	0.391	Eye Corrosion:	0.035
Eye Irritation:	0.912	Respiratory Toxicity:	0.321
Drug-induced Neurotoxicity:	0.75	Ototoxicity:	0.593
Hematotoxicity:	0.437	Drug-induced Nephrotoxicity:	0.719
Genotoxicity:	0.084	RPMI-8226 Immunitoxicity:	0.123
A549 Cytotoxicity:	0.252	Hek293 Cytotoxicity:	0.383
BCF:	1.075 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.554 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.078 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.305 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	fruit	n.a.	PMID[15739361]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	seed	n.a.	PMID[23845552]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	seeds	n.a.	n.a.	PMID[23999046]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	11

Activity Type	# Activity
Cell line	10
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT171	Cell line	MRC5	Homo sapiens	IC50	>	50000.0	nM	PMID[16038541]
NPT111	Cell line	K562	Homo sapiens	IC50	>	50000.0	nM	PMID[10780915]
NPT466	Cell line	U-937	Homo sapiens	IC50	>	50000.0	nM	PMID[18247573]
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	27390.0	nM	PMID[21130542]
NPT453	Cell line	HT-1080	Homo sapiens	IC50	=	36350.0	nM	PMID[18672931]
NPT81	Cell line	A549	Homo sapiens	IC50	>	50000.0	nM	PMID[25938459]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	35960.0	nM	PMID[21719287]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	50000.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	50000.0	nM	PMID[2016726]
NPT165	Cell line	HeLa	Homo sapiens	IC50	>	50000.0	nM	PMID[2016726]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	50000.0	nM	PMID[23999046]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC118787 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	17429
0.1-0.2	26764
0.2-0.3	4842
0.3-0.4	642
0.4-0.5	152
0.5-0.6	24
0.6-0.7	0
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8103	Intermediate Similarity	NPC249791
0.5867	Remote Similarity	NPC469888
0.5833	Remote Similarity	NPC482417
0.5714	Remote Similarity	NPC126206
0.5522	Remote Similarity	NPC147821
0.5522	Remote Similarity	NPC319625
0.5522	Remote Similarity	NPC183181
0.5522	Remote Similarity	NPC41706
0.5441	Remote Similarity	NPC476387
0.5441	Remote Similarity	NPC237594
0.5441	Remote Similarity	NPC119060
0.5439	Remote Similarity	NPC209567
0.5362	Remote Similarity	NPC224876
0.5316	Remote Similarity	NPC470413
0.5303	Remote Similarity	NPC58607
0.5303	Remote Similarity	NPC191037
0.5303	Remote Similarity	NPC135127
0.5303	Remote Similarity	NPC178284
0.5195	Remote Similarity	NPC469559
0.5147	Remote Similarity	NPC83375
0.5128	Remote Similarity	NPC107145
0.5072	Remote Similarity	NPC302378
0.507	Remote Similarity	NPC209985
0.5065	Remote Similarity	NPC480700
0.5063	Remote Similarity	NPC473909

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC118787 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3612
0.1-0.2	5324
0.2-0.3	204
0.3-0.4	6
0.4-0.5	4
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data