NPASS Compound

Natural Product: NPC479644

Natural Product ID	NPC479644
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	XMTUODQQJGUHQG-PFFISDNPSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	71456925
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001615] Flavones [CHEMONTID:0003503] 6-prenylated flavones

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 65 68 0 0 0 0 0 0 0 0999 V2000 0.1480 -1.4767 -1.8465 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8541 -1.1637 -3.1033 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2679 -0.4557 -4.0299 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0420 0.1317 -4.0741 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0077 0.0357 -3.0137 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7362 -1.1082 -2.8157 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6762 -1.2177 -1.8265 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9340 -0.1667 -0.9757 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2194 0.9964 -1.1487 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5002 2.0303 -0.2801 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9062 3.1101 -0.3637 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4762 1.8543 0.7145 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1564 0.6699 0.8377 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1711 0.4635 1.8592 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4894 1.4426 2.7561 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4699 1.2290 3.7347 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1373 0.0431 3.8258 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8182 -0.9563 2.9164 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8537 -0.7300 1.9629 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1153 -0.1743 4.7995 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8475 -0.2821 -0.0183 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2756 1.1016 -2.1442 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5835 2.3016 -2.2730 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5374 -2.2382 -3.6466 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2843 -1.6792 -3.3054 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1159 -1.1573 -2.2896 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2600 0.2122 -2.1554 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6290 0.9457 -2.9630 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1165 0.8198 -1.1111 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7463 -0.0291 -0.3029 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6103 0.4607 0.7546 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8331 1.7936 0.9982 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6797 2.2193 2.0325 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3137 1.3010 2.8354 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0982 -0.0560 2.6012 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2605 -0.4500 1.5776 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7452 -0.9656 3.4197 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5939 -2.3624 3.2647 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1551 1.7060 3.8633 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4243 -2.4280 -1.8964 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9958 -1.7712 -1.1276 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3192 -0.6524 -1.3261 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9386 -0.3018 -4.9343 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8677 1.2639 -4.2195 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5483 -0.0720 -5.1053 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2546 -2.1404 -1.6759 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6947 2.6669 1.3949 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0303 2.4065 2.7762 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7193 2.0111 4.4456 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3585 -1.9022 2.9966 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6287 -1.5241 1.2720 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0882 -0.0672 4.5408 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8529 2.5804 -1.6337 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5978 -2.3466 -3.9911 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6851 -1.3485 -4.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2098 -2.7648 -3.3083 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1964 1.8911 -1.0451 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6268 -1.1064 -0.4182 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3646 2.5552 0.4036 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8294 3.2828 2.1925 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0909 -1.5175 1.3935 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6503 -2.6331 3.7790 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5499 -2.6733 2.2135 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4141 -2.8938 3.7942 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0744 1.2865 3.9758 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 17 20 1 0 13 21 1 0 9 22 2 0 22 23 1 0 6 24 1 0 2 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 35 37 1 0 37 38 1 0 34 39 1 0 22 5 1 0 36 31 1 0 21 8 1 0 19 14 1 0 1 40 1 0 1 41 1 0 1 42 1 0 3 43 1 0 4 44 1 0 4 45 1 0 7 46 1 0 12 47 1 0 15 48 1 0 16 49 1 0 18 50 1 0 19 51 1 0 20 52 1 0 23 53 1 0 24 54 1 0 25 55 1 0 25 56 1 0 29 57 1 0 30 58 1 0 32 59 1 0 33 60 1 0 36 61 1 0 38 62 1 0 38 63 1 0 38 64 1 0 39 65 1 0 M END

Standard InCHIKey	XMTUODQQJGUHQG-PFFISDNPSA-N
Standard InCHI	InChI=1S/C30H26O9/c1-17(16-38-28(35)12-5-18-4-11-22(32)26(13-18)37-2)3-10-21-23(33)14-27-29(30(21)36)24(34)15-25(39-27)19-6-8-20(31)9-7-19/h3-9,11-15,31-33,36H,10,16H2,1-2H3/b12-5+,17-3+
SMILES	C/C(=CCc1c(cc2c(c(=O)cc(c3ccc(cc3)O)o2)c1O)O)/COC(=O)/C=C/c1ccc(c(c1)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	530.16	Volume:	535.412 ? Van der Waals volume.
Dense:	0.99	LogP:	3.994 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.06 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.894 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	27.0
TPSA:	146.66 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.14	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.976	Fsp³:	0.133
MCE-18:	26.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.974 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.989 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.997 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.092	Promiscuous compounds:	0.24

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.347	MDCK Permeability:	-4.847
Pgp-inhibitor:	0.842	Pgp-substrate:	0.005
PAMPA:	0.066 ? 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):	0.008
20% Bioavailability (F20%):	0.972	30% Bioavailability (F30%):	0.987
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.166
Plasma Protein Binding (PPB):	97.685%	Volume Distribution (VD):	-0.135
Fu:	2.114% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.956
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.01	CYP1A2-substrate:	0.513
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.006
CYP2C9-inhibitor:	0.115	CYP2C9-substrate:	0.087
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.998
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.894 ? 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):

3.804

Half-life (T1/2):

1.463

ADMET: Toxicity

hERG Blockers:	0.089	hERG Blockers (10um):	0.57
Human Hepatotoxicity (H-HT):	0.591	Drug-induced Liver Injury (DILI):	0.807
AMES Toxicity:	0.646	Rat Oral Acute Toxicity:	0.537
Maximum Recommended Daily Dose:	0.96	Skin Sensitization:	0.982
Carcinogencity:	0.5	Eye Corrosion:	0.0
Eye Irritation:	0.879	Respiratory Toxicity:	0.877
Drug-induced Neurotoxicity:	0.039	Ototoxicity:	0.158
Hematotoxicity:	0.04	Drug-induced Nephrotoxicity:	0.127
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.217
A549 Cytotoxicity:	0.785	Hek293 Cytotoxicity:	0.966
BCF:	1.226 ? 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:	4.66 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.646 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.408 ? 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
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	n.a.	root	n.a.	DOI[10.1016/0031-9422(95)00135-T]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	Wood	n.a.	n.a.	PMID[23113717]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	n.a.	formosan	n.a.	PMID[8864236]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	Latex Exudate	n.a.	n.a.	Database[FooDB]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17767	Artocarpus heterophyllus	Species	Moraceae	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	1

Activity Type	# Activity
Others	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
NPT2	Others	Unspecified	n.a.	IC50	=	40000.0	nM	PMID[23113717]

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 NPC479644 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	17164
0.1-0.2	27321
0.2-0.3	4558
0.3-0.4	699
0.4-0.5	100
0.5-0.6	13
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8642	High Similarity	NPC479643
0.5909	Remote Similarity	NPC602497
0.5904	Remote Similarity	NPC284220
0.5806	Remote Similarity	NPC479646
0.5806	Remote Similarity	NPC155253
0.5632	Remote Similarity	NPC189706
0.5408	Remote Similarity	NPC35598
0.5408	Remote Similarity	NPC222689
0.5364	Remote Similarity	NPC472993
0.5155	Remote Similarity	NPC479647
0.5114	Remote Similarity	NPC3825
0.5111	Remote Similarity	NPC306488
0.5083	Remote Similarity	NPC199172
0.5056	Remote Similarity	NPC486096

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479644 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3219
0.1-0.2	5842
0.2-0.3	84
0.3-0.4	5
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