NPASS Compound

Natural Product: NPC181014

Natural Product ID	NPC181014
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KUBUHOMBTJDYAN-FUQZIJMVSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	101265354
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003540] Flavonoid-8-O-glycosides

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 54 57 0 0 0 0 0 0 0 0999 V2000 4.1779 0.3844 0.8881 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7287 1.5915 0.4635 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9502 2.7224 0.3883 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6211 2.6550 0.7354 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0950 1.4542 1.1524 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8439 0.3022 1.2400 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2342 -0.9589 1.6925 C 0 0 2 0 0 0 0 0 0 0 0 0 3.1328 -2.1477 1.5700 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2011 -2.5357 0.1299 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2650 -2.8479 -0.4515 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9537 -2.5440 -0.6155 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8048 -3.2056 -1.8182 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6270 -3.2141 -2.5230 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4683 -2.5415 -2.0310 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3495 -1.8746 -0.8375 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8517 -1.8737 -0.1316 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9815 -1.2018 1.0771 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3942 -1.1877 -0.2943 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6807 0.1938 -0.4829 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9796 0.4495 -1.1815 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3270 1.9032 -0.9272 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6319 1.9758 0.5564 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5776 1.3170 1.3833 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2246 0.2234 2.2057 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3131 0.7263 2.9120 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5335 0.7856 0.7184 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7603 3.3226 0.8781 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4397 2.3007 -1.6534 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8698 0.2793 -2.5625 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6876 -2.5439 -2.7475 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9398 -3.8811 -2.2917 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5052 3.9353 -0.0388 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8415 -0.4677 0.9251 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7759 1.6602 0.1863 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0374 3.5698 0.6631 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0404 1.4576 1.4144 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0152 -0.8300 2.7901 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0987 -1.9933 2.0415 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6385 -2.9982 2.0870 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5831 -3.7526 -3.4565 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8739 0.5355 -1.2038 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8337 -0.1405 -0.7673 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4387 2.5330 -1.1139 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6193 1.4974 0.6974 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1927 2.0663 2.1194 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5697 -0.6104 1.5622 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4488 -0.1889 2.9121 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1709 0.5635 2.4708 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6721 3.6720 0.7490 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2232 2.1943 -2.6150 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6984 -0.1403 -2.8954 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5215 -2.8285 -2.2690 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1126 -3.9750 -3.2846 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4431 4.2117 0.2611 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 1 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 15 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 1 0 23 26 1 0 22 27 1 0 21 28 1 0 20 29 1 0 14 30 1 0 12 31 1 0 3 32 1 0 6 1 1 0 17 7 1 0 26 19 1 0 16 11 1 0 1 33 1 0 2 34 1 0 4 35 1 0 5 36 1 0 7 37 1 1 8 38 1 0 8 39 1 0 13 40 1 0 19 41 1 6 20 42 1 1 21 43 1 1 22 44 1 6 23 45 1 1 24 46 1 0 24 47 1 0 25 48 1 0 27 49 1 0 28 50 1 0 29 51 1 0 30 52 1 0 31 53 1 0 32 54 1 0 M END

Standard InCHIKey	KUBUHOMBTJDYAN-FUQZIJMVSA-N
Standard InCHI	InChI=1S/C21H22O11/c22-7-14-16(27)17(28)18(29)21(31-14)32-19-12(26)5-10(24)15-11(25)6-13(30-20(15)19)8-1-3-9(23)4-2-8/h1-5,13-14,16-18,21-24,26-29H,6-7H2/t13-,14+,16+,17-,18+,21-/m0/s1
SMILES	c1cc(ccc1[C@@H]1CC(=O)c2c(cc(c(c2O1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	450.12	Volume:	415.784 ? Van der Waals volume.
Dense:	1.083	LogP:	0.71 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.2 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.038 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	186.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.324	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.183	Fsp³:	0.381
MCE-18:	90.552 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.606	Fluc inhibitor:	0.397 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.115 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.289 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.226	Promiscuous compounds:	0.322

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.663	MDCK Permeability:	-4.982
Pgp-inhibitor:	0.01	Pgp-substrate:	0.115
PAMPA:	0.977 ? 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):	0.03
20% Bioavailability (F20%):	0.004	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.279
Plasma Protein Binding (PPB):	88.151%	Volume Distribution (VD):	-0.124
Fu:	10.754% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.986
BSEP inhibitor:	0.013

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.327
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.949
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.295
HLM stability:	0.427 ? 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):

2.742

Half-life (T1/2):

3.506

ADMET: Toxicity

hERG Blockers:	0.023	hERG Blockers (10um):	0.112
Human Hepatotoxicity (H-HT):	0.817	Drug-induced Liver Injury (DILI):	0.586
AMES Toxicity:	0.898	Rat Oral Acute Toxicity:	0.056
Maximum Recommended Daily Dose:	0.064	Skin Sensitization:	0.996
Carcinogencity:	0.173	Eye Corrosion:	0.0
Eye Irritation:	0.673	Respiratory Toxicity:	0.003
Drug-induced Neurotoxicity:	0.078	Ototoxicity:	0.923
Hematotoxicity:	0.169	Drug-induced Nephrotoxicity:	0.826
Genotoxicity:	0.951	RPMI-8226 Immunitoxicity:	0.157
A549 Cytotoxicity:	0.438	Hek293 Cytotoxicity:	0.484
BCF:	0.416 ? 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:	2.949 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.378 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.64 ? 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
NPO40820	Corispermum marschallii	Species	n.a.	n.a.	Aerial Parts	n.a.	n.a.	PMID[30109803]

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	3

Activity Type	# Activity
Cell line	3

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
NPT2740	Cell line	Neutrophils	n.a.	IC50	=	13200.0	nM	PMID[30109803]
NPT2740	Cell line	Neutrophils	n.a.	IC50	=	11400.0	nM	PMID[30109803]
NPT2740	Cell line	Neutrophils	n.a.	IC50	=	23700.0	nM	PMID[30109803]

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 NPC181014 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	17710
0.1-0.2	27028
0.2-0.3	3903
0.3-0.4	1009
0.4-0.5	174
0.5-0.6	25
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
0.6986	Remote Similarity	NPC39351
0.6533	Remote Similarity	NPC26195
0.6486	Remote Similarity	NPC169248
0.6486	Remote Similarity	NPC72649
0.6316	Remote Similarity	NPC471457
0.6234	Remote Similarity	NPC206378
0.6092	Remote Similarity	NPC168789
0.5974	Remote Similarity	NPC97052
0.5974	Remote Similarity	NPC170475
0.5974	Remote Similarity	NPC46067
0.5949	Remote Similarity	NPC29830
0.5926	Remote Similarity	NPC236934
0.5897	Remote Similarity	NPC219163
0.5714	Remote Similarity	NPC186595
0.561	Remote Similarity	NPC472381
0.561	Remote Similarity	NPC472383
0.557	Remote Similarity	NPC45400
0.5375	Remote Similarity	NPC259182
0.5301	Remote Similarity	NPC5778
0.5238	Remote Similarity	NPC477502
0.5204	Remote Similarity	NPC321916
0.5185	Remote Similarity	NPC88484
0.5176	Remote Similarity	NPC479540
0.5132	Remote Similarity	NPC199335
0.5132	Remote Similarity	NPC477240
0.5128	Remote Similarity	NPC121001
0.5111	Remote Similarity	NPC142860
0.5111	Remote Similarity	NPC152538
0.5111	Remote Similarity	NPC246469
0.5111	Remote Similarity	NPC89088
0.5065	Remote Similarity	NPC190217
0.506	Remote Similarity	NPC225445

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC181014 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4496
0.1-0.2	4551
0.2-0.3	85
0.3-0.4	15
0.4-0.5	3
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