NPASS Compound

Natural Product: NPC474998

Natural Product ID	NPC474998
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Xanthoangelol J
IUPAC Name	(E)-1-[2,4-dihydroxy-3-(3-hydroxy-3,7-dimethyloct-6-enyl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one
Synonyms	xanthoangelol J
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL491512
PubChem CID	11675925
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003467] Linear 1,3-diarylpropanoids [CHEMONTID:0001630] Chalcones and dihydrochalcones [CHEMONTID:0003509] 3-prenylated chalcones

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 60 61 0 0 0 0 0 0 0 0999 V2000 -7.3928 -0.0947 -2.9782 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2040 0.0292 -1.5141 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1014 0.5792 -1.0378 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8450 0.7358 0.4070 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6272 0.0368 0.9057 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3447 0.4674 0.2804 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0460 1.9325 0.4865 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2292 -0.2871 1.0418 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8924 0.0619 0.5054 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2477 -0.5896 1.1448 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1086 -1.4636 2.1864 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2606 -2.0116 2.7020 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4887 -1.6840 2.1812 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6652 -0.7929 1.1151 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5167 -0.2566 0.6131 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5611 0.6396 -0.4430 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0332 -0.5108 0.6234 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9189 -1.1478 1.2956 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3736 0.3473 -0.4513 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4706 0.7132 -0.9663 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8754 0.5180 -0.7983 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5308 0.0091 0.2931 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9155 -0.2244 0.3261 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6596 0.0717 -0.7878 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0650 0.5866 -1.9145 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7174 0.7908 -1.8880 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0352 -0.1386 -0.8139 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1422 -1.7937 2.7126 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2479 0.1845 -1.0757 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2557 -0.4657 -0.5888 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7587 -1.1461 -3.1558 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4681 0.1156 -3.5363 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2142 0.5992 -3.2809 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3574 0.9291 -1.7381 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8645 1.8132 0.7224 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7204 0.2804 0.9512 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7336 -1.0527 0.7576 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5548 0.2052 1.9907 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9461 2.5635 0.4986 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5288 2.1017 1.4594 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4208 2.3198 -0.3696 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3890 0.0272 2.0927 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4295 -1.3710 0.8622 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8140 -0.1253 -0.5858 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7467 1.1634 0.6295 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1603 -2.7069 3.5296 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3958 -2.1355 2.6105 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1284 0.3418 -1.3218 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4681 0.7975 -0.9642 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2637 1.4669 -1.8390 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0149 -0.1925 1.1975 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4202 -0.6257 1.1866 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6436 0.8249 -2.7996 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2667 1.1929 -2.7854 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5399 0.0157 0.0640 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4515 -2.7445 2.5734 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4128 -0.7653 -1.2807 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8773 -1.3040 0.0575 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6313 0.3425 0.0720 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0970 -0.8831 -1.1603 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 14 17 1 0 17 18 2 0 17 19 1 0 19 20 2 3 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 24 27 1 0 11 28 1 0 6 29 1 0 2 30 1 0 15 10 1 0 26 21 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 7 39 1 0 7 40 1 0 7 41 1 0 8 42 1 0 8 43 1 0 9 44 1 0 9 45 1 0 12 46 1 0 13 47 1 0 16 48 1 0 19 49 1 0 20 50 1 0 22 51 1 0 23 52 1 0 25 53 1 0 26 54 1 0 27 55 1 0 28 56 1 0 29 57 1 0 30 58 1 0 30 59 1 0 30 60 1 0 M END

Standard InCHIKey	BQRLJINJRBLFJV-XYOKQWHBSA-N
Standard InCHI	InChI=1S/C25H30O5/c1-17(2)5-4-15-25(3,30)16-14-21-23(28)13-11-20(24(21)29)22(27)12-8-18-6-9-19(26)10-7-18/h5-13,26,28-30H,4,14-16H2,1-3H3/b12-8+
SMILES	CC(=CCCC(C)(CCC1=C(C=CC(=C1O)C(=O)C=CC2=CC=C(C=C2)O)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	410.21	Volume:	444.066 ? Van der Waals volume.
Dense:	0.924	LogP:	4.969 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.416 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.096 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	15.0
TPSA:	97.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.261	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.261	Fsp³:	0.32
MCE-18:	34.0 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.986	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.417 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.541 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.532	Promiscuous compounds:	0.213

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.188	MDCK Permeability:	-4.771
Pgp-inhibitor:	0.117	Pgp-substrate:	0.005
PAMPA:	0.61 ? 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):	0.009
20% Bioavailability (F20%):	0.707	30% Bioavailability (F30%):	0.811
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.613
Plasma Protein Binding (PPB):	95.739%	Volume Distribution (VD):	0.31
Fu:	5.658% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.221
BSEP inhibitor:	0.652

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.977
CYP2C19-inhibitor:	0.006	CYP2C19-substrate:	0.971
CYP2C9-inhibitor:	0.56	CYP2C9-substrate:	0.887
CYP2D6-inhibitor:	0.992	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.781
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.787 ? 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):

7.951

Half-life (T1/2):

1.128

ADMET: Toxicity

hERG Blockers:	0.252	hERG Blockers (10um):	0.699
Human Hepatotoxicity (H-HT):	0.583	Drug-induced Liver Injury (DILI):	0.006
AMES Toxicity:	0.227	Rat Oral Acute Toxicity:	0.032
Maximum Recommended Daily Dose:	0.424	Skin Sensitization:	0.996
Carcinogencity:	0.043	Eye Corrosion:	0.013
Eye Irritation:	0.974	Respiratory Toxicity:	0.738
Drug-induced Neurotoxicity:	0.195	Ototoxicity:	0.577
Hematotoxicity:	0.034	Drug-induced Nephrotoxicity:	0.521
Genotoxicity:	0.011	RPMI-8226 Immunitoxicity:	0.1
A549 Cytotoxicity:	0.23	Hek293 Cytotoxicity:	0.492
BCF:	1.549 ? 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:	4.579 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.894 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.476 ? 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
NPO21056	Angelica keiskei	Species	Apiaceae	Eukaryota	exudates	n.a.	n.a.	PMID[16441065]
NPO21056	Angelica keiskei	Species	Apiaceae	Eukaryota	stems	n.a.	n.a.	PMID[18558745]
NPO21056	Angelica keiskei	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21824777]
NPO21056	Angelica keiskei	Species	Apiaceae	Eukaryota	stems	n.a.	n.a.	PMID[25891102]
NPO21056	Angelica keiskei	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21056	Angelica keiskei	Species	Apiaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO21056	Angelica keiskei	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21056	Angelica keiskei	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21056	Angelica keiskei	Species	Apiaceae	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
Activity	5
IC50	1
Ratio	1

Activity Type	# Activity
Cell line	1
Others	6

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
NPT80	Cell line	Raji	Homo sapiens	Activity	=	70.0	%	PMID[16872140]
NPT2	Others	Unspecified	n.a.	Activity	=	0.0	%	PMID[17132069]
NPT2	Others	Unspecified	n.a.	Activity	=	12.5	%	DrugMatrix in vitro pharmacology data
NPT2	Others	Unspecified	n.a.	Activity	=	66.8	%	PMID[18183025]
NPT2	Others	Unspecified	n.a.	Activity	=	90.2	%	DOI[10.6019/CHEMBL1201861]
NPT2	Others	Unspecified	n.a.	IC50	=	264.0	molar ratio	PMID[15497935]
NPT2	Others	Unspecified	n.a.	Ratio	=	2.4	n.a.	PMID[25871261]

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 NPC474998 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	13288
0.1-0.2	31714
0.2-0.3	4433
0.3-0.4	326
0.4-0.5	65
0.5-0.6	23
0.6-0.7	7
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	Natural Product ID
0.6935	Remote Similarity	NPC484873
0.6885	Remote Similarity	NPC266689
0.6667	Remote Similarity	NPC72158
0.6333	Remote Similarity	NPC213485
0.623	Remote Similarity	NPC479645
0.623	Remote Similarity	NPC479648
0.6061	Remote Similarity	NPC21305
0.5909	Remote Similarity	NPC264112
0.5833	Remote Similarity	NPC62952
0.5735	Remote Similarity	NPC19622
0.5735	Remote Similarity	NPC112789
0.5735	Remote Similarity	NPC475042
0.5645	Remote Similarity	NPC59319
0.5574	Remote Similarity	NPC475733
0.5556	Remote Similarity	NPC100067
0.5556	Remote Similarity	NPC481727
0.5556	Remote Similarity	NPC481726
0.5507	Remote Similarity	NPC470210
0.5484	Remote Similarity	NPC478710
0.5455	Remote Similarity	NPC473017
0.5397	Remote Similarity	NPC162612
0.5373	Remote Similarity	NPC21350
0.5352	Remote Similarity	NPC484872
0.5323	Remote Similarity	NPC30501
0.5294	Remote Similarity	NPC23126
0.5179	Remote Similarity	NPC19174
0.5179	Remote Similarity	NPC115159
0.5135	Remote Similarity	NPC275903
0.5072	Remote Similarity	NPC608784
0.507	Remote Similarity	NPC274109

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474998 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3833
0.1-0.2	5171
0.2-0.3	146
0.3-0.4	0
0.4-0.5	0
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