NPASS Compound

Natural Product: NPC40323

Natural Product ID	NPC40323
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JXWGCVLNCGCZRU-JENRNSKYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11641481
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0002934] Flavonoid O-glucuronides [CHEMONTID:0003534] Flavonoid-7-O-glucuronides

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 52 55 0 0 0 0 0 0 0 0999 V2000 5.6422 -0.2248 -0.3512 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5112 -1.0456 0.3917 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0380 -1.9385 1.3168 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6733 -1.9916 1.4820 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8291 -1.1872 0.7534 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2931 -0.2646 -0.2004 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2956 0.5266 -0.9031 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6418 1.4529 -1.8496 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6480 2.1989 -2.5078 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0194 3.0310 -3.3630 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3475 1.9446 -2.1492 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3636 2.6659 -2.7837 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9382 2.4240 -2.4374 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3164 1.4768 -1.4675 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2858 0.7893 -0.8704 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0460 0.9928 -1.1811 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0073 0.3387 -0.6115 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6535 1.3021 -1.1849 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1268 0.4061 -0.2584 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0176 1.0880 0.8014 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1663 0.0758 1.9175 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8771 -1.1333 1.3335 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1769 -1.5502 0.0858 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8545 -2.7413 -0.5181 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1116 -3.7692 0.1401 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2311 -2.7431 -1.8709 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0054 -0.5512 -0.8367 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7044 -2.1715 2.2753 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8578 0.5943 3.0052 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4747 2.2770 1.2175 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6561 3.6260 -3.7594 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9516 1.7138 -2.2155 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1959 -2.9019 2.4247 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8835 -2.7597 2.0620 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0700 0.4524 -1.0586 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5783 -0.9816 0.2403 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7597 -1.2574 0.9111 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7056 2.9949 -2.9404 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4965 0.0333 -0.1037 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3921 -0.2078 0.2903 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9803 1.2909 0.2861 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1782 -0.2329 2.2566 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9589 -0.9855 1.2256 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1547 -1.9191 0.3894 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0988 -3.5834 -2.4449 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2248 -1.8890 3.0754 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7263 0.9957 2.7571 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6273 2.4158 2.1772 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2558 4.5401 -3.7657 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2151 2.6676 -2.4316 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7011 -3.1600 3.2570 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7182 -3.1252 1.5789 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 14 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 23 27 1 0 22 28 1 0 21 29 1 0 20 30 1 0 12 31 1 0 8 32 1 0 4 33 1 0 3 34 1 0 6 1 1 0 17 7 1 0 27 19 1 0 16 11 1 0 1 35 1 0 2 36 1 0 5 37 1 0 13 38 1 0 15 39 1 0 19 40 1 1 20 41 1 6 21 42 1 1 22 43 1 6 23 44 1 1 26 45 1 0 28 46 1 0 29 47 1 0 30 48 1 0 31 49 1 0 32 50 1 0 33 51 1 0 34 52 1 0 M END

Standard InCHIKey	JXWGCVLNCGCZRU-JENRNSKYSA-N
Standard InCHI	InChI=1S/C21H18O13/c22-8-2-1-6(3-9(8)23)18-15(27)13(25)12-10(24)4-7(5-11(12)33-18)32-21-17(29)14(26)16(28)19(34-21)20(30)31/h1-5,14,16-17,19,21-24,26-29H,(H,30,31)/t14-,16-,17+,19-,21+/m0/s1
SMILES	c1cc(c(cc1c1c(c(=O)c2c(cc(cc2o1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](C(=O)O)O1)O)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	478.07	Volume:	428.091 ? Van der Waals volume.
Dense:	1.117	LogP:	0.363 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.012 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.77 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	25.0
TPSA:	227.58 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.223	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.083	Fsp³:	0.238
MCE-18:	94.769 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.51	Fluc inhibitor:	0.326 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.958 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.844 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.319	Promiscuous compounds:	0.554

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.736	MDCK Permeability:	-4.947
Pgp-inhibitor:	0.0	Pgp-substrate:	0.046
PAMPA:	1.0 ? 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):	0.699
20% Bioavailability (F20%):	0.208	30% Bioavailability (F30%):	0.97
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.88
Plasma Protein Binding (PPB):	81.973%	Volume Distribution (VD):	-0.235
Fu:	16.366% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.49
OATP1B3 inhibitor:	0.986	BCRP inhibitor:	0.116
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.008
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.662
HLM stability:	0.287 ? 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):

1.999

Half-life (T1/2):

4.218

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.068
Human Hepatotoxicity (H-HT):	0.3	Drug-induced Liver Injury (DILI):	0.976
AMES Toxicity:	0.551	Rat Oral Acute Toxicity:	0.079
Maximum Recommended Daily Dose:	0.079	Skin Sensitization:	0.991
Carcinogencity:	0.024	Eye Corrosion:	0.0
Eye Irritation:	0.871	Respiratory Toxicity:	0.058
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.694
Hematotoxicity:	0.036	Drug-induced Nephrotoxicity:	0.226
Genotoxicity:	0.825	RPMI-8226 Immunitoxicity:	0.059
A549 Cytotoxicity:	0.436	Hek293 Cytotoxicity:	0.104
BCF:	0.3 ? 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:	2.921 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.276 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.602 ? 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
NPO2878	Conyza pyrifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8112	Acacia intertexta	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7568	Mora excelsa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8112	Acacia intertexta	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2878	Conyza pyrifolia	Species	Asteraceae	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

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

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 NPC40323 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	23958
0.1-0.2	23354
0.2-0.3	1834
0.3-0.4	543
0.4-0.5	121
0.5-0.6	29
0.6-0.7	15
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
0.7895	Intermediate Similarity	NPC20505
0.7215	Intermediate Similarity	NPC282169
0.7215	Intermediate Similarity	NPC49344
0.6923	Remote Similarity	NPC238376
0.6835	Remote Similarity	NPC277205
0.6835	Remote Similarity	NPC37919
0.6707	Remote Similarity	NPC608742
0.6386	Remote Similarity	NPC235260
0.6386	Remote Similarity	NPC155763
0.6286	Remote Similarity	NPC87125
0.6118	Remote Similarity	NPC610187
0.6098	Remote Similarity	NPC108831
0.6098	Remote Similarity	NPC182634
0.6067	Remote Similarity	NPC67105
0.6024	Remote Similarity	NPC323593
0.6024	Remote Similarity	NPC203500
0.6	Remote Similarity	NPC135277
0.6	Remote Similarity	NPC253685
0.5747	Remote Similarity	NPC43211
0.5698	Remote Similarity	NPC138927
0.5632	Remote Similarity	NPC285197
0.5618	Remote Similarity	NPC601586
0.5579	Remote Similarity	NPC229409
0.5455	Remote Similarity	NPC307938
0.5455	Remote Similarity	NPC237435
0.5455	Remote Similarity	NPC210094
0.5405	Remote Similarity	NPC143799
0.5405	Remote Similarity	NPC605755
0.5393	Remote Similarity	NPC115760
0.5393	Remote Similarity	NPC486578
0.5385	Remote Similarity	NPC600989
0.5376	Remote Similarity	NPC275454
0.5376	Remote Similarity	NPC227508
0.5349	Remote Similarity	NPC19709
0.5287	Remote Similarity	NPC136042
0.5287	Remote Similarity	NPC189142
0.5287	Remote Similarity	NPC77660
0.5227	Remote Similarity	NPC245014
0.5227	Remote Similarity	NPC84362
0.5227	Remote Similarity	NPC271692
0.5169	Remote Similarity	NPC101191
0.5169	Remote Similarity	NPC117260
0.5152	Remote Similarity	NPC80068
0.5128	Remote Similarity	NPC252933
0.5067	Remote Similarity	NPC152042
0.5065	Remote Similarity	NPC200740
0.5052	Remote Similarity	NPC64051

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC40323 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4358
0.1-0.2	4721
0.2-0.3	62
0.3-0.4	6
0.4-0.5	2
0.5-0.6	1
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
0.5455	Remote Similarity	NPD4338	Clinical (unspecified phase)

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