NPASS Compound

Natural Product: NPC603508

Natural Product ID	NPC603508
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	SVIMIMQAVRQGEK-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1208793
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 64 69 0 0 0 0 0 0 0 0999 V2000 7.7617 2.1823 2.3600 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5298 2.6599 1.0700 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4419 2.3699 0.2831 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4009 2.9514 -0.9790 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3167 2.6696 -1.7785 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2715 3.2468 -3.0370 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3011 1.8341 -1.3383 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2094 1.5420 -2.1256 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1701 2.0677 -3.2695 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2249 0.7089 -1.6506 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3065 0.1547 -0.3935 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2720 -0.7410 0.1478 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4352 -1.2550 1.4250 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5159 -2.1035 2.0153 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6234 -2.4458 1.2721 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5242 -3.2989 1.8954 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8122 -1.9511 0.0022 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0044 -2.3317 -0.7287 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0035 -3.4506 -1.5304 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8303 -4.1879 -1.6079 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8239 -5.3343 -2.4273 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1560 -3.7758 -2.2066 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2875 -2.9861 -2.0755 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4552 -3.2961 -2.7467 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2966 -1.8554 -1.2685 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4107 -1.0623 -1.1282 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4687 -1.3447 -1.7374 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2819 0.0470 -0.2835 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1052 0.3248 0.3681 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9909 1.5020 1.2559 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0084 2.3669 1.4845 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8108 3.4391 2.3290 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6152 3.6898 2.9685 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4427 4.7896 3.8232 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5962 2.7914 2.7164 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7766 1.7168 1.8768 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0737 -0.4754 0.1909 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1397 -1.5257 -0.5874 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1454 -1.1088 -0.5263 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3675 0.4651 0.3165 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3305 1.2506 -0.0868 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4176 1.5347 0.7114 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8565 2.1216 2.5261 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3843 2.9027 3.1385 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3322 1.1932 2.5346 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2060 3.5989 -1.2972 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4296 4.2327 -3.1746 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3750 0.4956 -2.2929 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3246 -0.9697 1.9676 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6871 -2.4790 3.0148 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2603 -3.9186 2.6261 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2106 -5.7310 -2.5802 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2563 -5.1706 -3.4249 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4110 -6.1193 -1.9302 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1410 -4.6572 -2.8327 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8383 -4.2526 -2.7668 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1725 0.6624 -0.1848 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9799 2.2318 1.0141 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6310 4.1478 2.5216 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8724 5.5776 3.5830 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6402 2.9759 3.2163 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9298 1.0282 1.7088 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0254 -0.7361 -1.5192 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4717 1.0908 1.7041 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 5 7 2 0 7 8 1 0 8 9 2 0 8 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 15 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 19 22 1 0 22 23 2 0 23 24 1 0 23 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 33 35 1 0 35 36 2 0 29 37 1 0 37 38 1 0 17 39 2 0 11 40 1 0 40 41 1 0 41 42 2 0 42 3 1 0 41 7 1 0 39 12 1 0 38 18 1 0 38 25 2 0 36 30 1 0 1 43 1 0 1 44 1 0 1 45 1 0 4 46 1 0 6 47 1 0 10 48 1 0 13 49 1 0 14 50 1 0 16 51 1 0 21 52 1 0 21 53 1 0 21 54 1 0 22 55 1 0 24 56 1 0 28 57 1 0 31 58 1 0 32 59 1 0 34 60 1 0 35 61 1 0 36 62 1 0 39 63 1 0 42 64 1 0 M END

Standard InCHIKey	SVIMIMQAVRQGEK-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C32H22O10/c1-39-18-10-21(35)30-22(36)12-26(41-28(30)11-18)16-5-8-20(34)19(9-16)29-27(40-2)14-24(38)31-23(37)13-25(42-32(29)31)15-3-6-17(33)7-4-15/h3-14,33-35,38H,1-2H3
SMILES	COc1cc(O)c2c(=O)cc(-c3ccc(O)c(-c4c(OC)cc(O)c5c(=O)cc(-c6ccc(O)cc6)oc45)c3)oc2c1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	566.12	Volume:	556.408 ? Van der Waals volume.
Dense:	1.017	LogP:	4.196 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.707 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.343 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	36.0
TPSA:	159.8 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.203	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.998	Fsp³:	0.062
MCE-18:	36.0 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.995	Fluc inhibitor:	0.284 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.978 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.998 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.345	Promiscuous compounds:	0.897

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.974	MDCK Permeability:	-4.769
Pgp-inhibitor:	0.074	Pgp-substrate:	0.111
PAMPA:	0.116 ? 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):	0.003
20% Bioavailability (F20%):	0.328	30% Bioavailability (F30%):	0.851
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.847
Plasma Protein Binding (PPB):	97.39%	Volume Distribution (VD):	-0.244
Fu:	2.369% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.987
BSEP inhibitor:	0.992

ADMET: Metabolism

CYP1A2-inhibitor:	0.021	CYP1A2-substrate:	0.713
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.008
CYP2C9-inhibitor:	0.895	CYP2C9-substrate:	0.335
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.017
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.878 ? 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):

3.664

Half-life (T1/2):

1.465

ADMET: Toxicity

hERG Blockers:	0.085	hERG Blockers (10um):	0.483
Human Hepatotoxicity (H-HT):	0.473	Drug-induced Liver Injury (DILI):	0.99
AMES Toxicity:	0.747	Rat Oral Acute Toxicity:	0.618
Maximum Recommended Daily Dose:	0.962	Skin Sensitization:	0.383
Carcinogencity:	0.863	Eye Corrosion:	0.002
Eye Irritation:	0.982	Respiratory Toxicity:	0.892
Drug-induced Neurotoxicity:	0.011	Ototoxicity:	0.075
Hematotoxicity:	0.062	Drug-induced Nephrotoxicity:	0.032
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.134
A549 Cytotoxicity:	0.606	Hek293 Cytotoxicity:	0.934
BCF:	1.295 ? 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:	4.564 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.992 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.696 ? 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
NPO47795	Araucaria excelsa	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47372	Taiwania spp.	Genus	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO56873	Thuja gigantea	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47272	Thuja javanica	Genus	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	1

Activity Type	# Activity
Individual protein	1
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT740	Individual protein	Beta-secretase 1	Homo sapiens	IC50	=	6250.0	nM	PMID[20598535]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	52.6	%	PMID[26004578]

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 NPC603508 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	32815
0.1-0.2	14410
0.2-0.3	1880
0.3-0.4	516
0.4-0.5	184
0.5-0.6	28
0.6-0.7	14
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8923	High Similarity	NPC158027
0.8088	Intermediate Similarity	NPC290830
0.7971	Intermediate Similarity	NPC159707
0.7971	Intermediate Similarity	NPC194593
0.7541	Intermediate Similarity	NPC234133
0.75	Intermediate Similarity	NPC601565
0.7123	Intermediate Similarity	NPC121649
0.7042	Intermediate Similarity	NPC248739
0.6933	Remote Similarity	NPC265624
0.6818	Remote Similarity	NPC610914
0.6712	Remote Similarity	NPC601984
0.6447	Remote Similarity	NPC215203
0.6364	Remote Similarity	NPC108406
0.6364	Remote Similarity	NPC205026
0.6329	Remote Similarity	NPC55443
0.6324	Remote Similarity	NPC137062
0.6308	Remote Similarity	NPC127447
0.6308	Remote Similarity	NPC29353
0.6176	Remote Similarity	NPC124784
0.6104	Remote Similarity	NPC14606
0.6061	Remote Similarity	NPC52611
0.6053	Remote Similarity	NPC600972
0.5974	Remote Similarity	NPC303485
0.5974	Remote Similarity	NPC600396
0.5942	Remote Similarity	NPC195202
0.5897	Remote Similarity	NPC186227
0.5753	Remote Similarity	NPC138299
0.5735	Remote Similarity	NPC33265
0.5735	Remote Similarity	NPC48479
0.5714	Remote Similarity	NPC223579
0.557	Remote Similarity	NPC71061
0.5556	Remote Similarity	NPC18699
0.5507	Remote Similarity	NPC198826
0.5507	Remote Similarity	NPC143799
0.5507	Remote Similarity	NPC146679
0.5507	Remote Similarity	NPC120163
0.5493	Remote Similarity	NPC177298
0.5432	Remote Similarity	NPC39360
0.5432	Remote Similarity	NPC29763
0.5432	Remote Similarity	NPC210003
0.5429	Remote Similarity	NPC78913
0.5333	Remote Similarity	NPC111112
0.5309	Remote Similarity	NPC331652
0.5286	Remote Similarity	NPC250266
0.5238	Remote Similarity	NPC27942
0.519	Remote Similarity	NPC259757
0.5143	Remote Similarity	NPC241498
0.5139	Remote Similarity	NPC328119
0.5065	Remote Similarity	NPC291746
0.5062	Remote Similarity	NPC150908

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC603508 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6455
0.1-0.2	2643
0.2-0.3	45
0.3-0.4	6
0.4-0.5	1
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