NPASS Compound

Natural Product: NPC600972

Natural Product ID	NPC600972
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VFGDLHHMZWLHQG-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3589107
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 61 66 0 0 0 0 0 0 0 0999 V2000 -0.6644 3.9774 0.5682 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3001 2.7196 1.0701 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0546 1.5715 0.8477 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2154 1.6364 0.1069 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9764 0.4811 -0.1179 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0784 0.5342 -0.8193 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8380 -0.5125 -1.0669 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0563 -0.3987 -1.8544 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4167 0.8619 -2.3544 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5538 1.0537 -3.1080 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3961 0.0040 -3.4067 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5458 0.1883 -4.1665 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0525 -1.2379 -2.9212 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8956 -1.4383 -2.1534 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4510 -1.7277 -0.5601 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2844 -1.8251 0.1914 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9622 -2.9481 0.6376 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5238 -0.7031 0.4233 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3612 -0.7323 1.1574 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9447 -1.9440 1.6819 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5892 0.3802 1.3985 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6431 0.3516 2.1761 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8785 0.1265 1.6074 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0532 0.0966 2.3308 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3189 -0.1533 1.6161 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5427 -0.2031 2.2410 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7313 -0.4381 1.5673 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8402 -0.4856 2.1174 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6657 -0.6293 0.2032 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8195 -0.8721 -0.5519 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0604 -0.9205 0.0965 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7347 -1.0610 -1.9153 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4804 -0.9997 -2.4856 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3495 -1.1858 -3.8667 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3411 -0.7610 -1.7473 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4137 -0.5689 -0.3713 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3196 -0.3430 0.3145 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9719 0.3032 3.6855 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7434 0.5364 4.3152 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6025 0.5549 3.5402 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6116 0.7854 4.1631 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2348 4.6423 0.5839 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5114 4.4414 1.1096 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9070 3.8382 -0.5205 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5419 2.5741 -0.3016 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7635 1.6867 -2.1251 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8341 2.0257 -3.4951 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4368 0.4253 -3.7443 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7042 -2.0782 -3.1463 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6719 -2.4311 -1.7972 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0328 -2.6310 -0.7276 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3708 -2.5682 1.1401 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9046 -0.0320 0.5401 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5953 -0.0533 3.3109 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4216 -0.0363 0.4473 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6380 -1.2473 -2.4799 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8284 -0.6058 -4.5379 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3518 -0.7139 -2.2058 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8662 0.2867 4.2792 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6842 0.6986 5.3825 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4887 0.6696 3.6970 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 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 2 0 7 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 19 20 1 0 19 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 30 32 1 0 32 33 2 0 33 34 1 0 33 35 1 0 35 36 2 0 36 37 1 0 24 38 2 0 38 39 1 0 39 40 2 0 40 41 1 0 21 3 1 0 40 22 1 0 18 5 2 0 37 25 1 0 14 8 1 0 36 29 1 0 1 42 1 0 1 43 1 0 1 44 1 0 4 45 1 0 9 46 1 0 10 47 1 0 12 48 1 0 13 49 1 0 14 50 1 0 15 51 1 0 20 52 1 0 23 53 1 0 26 54 1 0 31 55 1 0 32 56 1 0 34 57 1 0 35 58 1 0 38 59 1 0 39 60 1 0 41 61 1 0 M END

Standard InCHIKey	VFGDLHHMZWLHQG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C31H20O10/c1-39-25-13-27-30(22(37)12-23(40-27)14-2-5-16(32)6-3-14)31(38)28(25)18-8-15(4-7-19(18)34)24-11-21(36)29-20(35)9-17(33)10-26(29)41-24/h2-13,32-35,38H,1H3
SMILES	COc1cc2oc(-c3ccc(O)cc3)cc(=O)c2c(O)c1-c1cc(-c2cc(=O)c3c(O)cc(O)cc3o2)ccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	552.11	Volume:	539.112 ? Van der Waals volume.
Dense:	1.024	LogP:	4.333 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.515 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.243 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	36.0
TPSA:	170.8 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.19	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.007	Fsp³:	0.032
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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.996	Fluc inhibitor:	0.624 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.95 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.994 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.513	Promiscuous compounds:	0.875

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.114	MDCK Permeability:	-4.803
Pgp-inhibitor:	0.002	Pgp-substrate:	0.269
PAMPA:	0.836 ? 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):	0.001
20% Bioavailability (F20%):	0.681	30% Bioavailability (F30%):	0.966
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.954
Plasma Protein Binding (PPB):	96.669%	Volume Distribution (VD):	-0.363
Fu:	2.71% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.952
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.98
BSEP inhibitor:	0.957

ADMET: Metabolism

CYP1A2-inhibitor:	0.054	CYP1A2-substrate:	0.42
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.82	CYP2C9-substrate:	0.662
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.014
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.213 ? 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):

3.054

Half-life (T1/2):

1.72

ADMET: Toxicity

hERG Blockers:	0.102	hERG Blockers (10um):	0.534
Human Hepatotoxicity (H-HT):	0.439	Drug-induced Liver Injury (DILI):	0.948
AMES Toxicity:	0.675	Rat Oral Acute Toxicity:	0.711
Maximum Recommended Daily Dose:	0.991	Skin Sensitization:	0.556
Carcinogencity:	0.839	Eye Corrosion:	0.002
Eye Irritation:	0.994	Respiratory Toxicity:	0.849
Drug-induced Neurotoxicity:	0.009	Ototoxicity:	0.049
Hematotoxicity:	0.025	Drug-induced Nephrotoxicity:	0.008
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.086
A549 Cytotoxicity:	0.739	Hek293 Cytotoxicity:	0.98
BCF:	1.241 ? 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:	4.437 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.793 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.576 ? 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
NPO56828	Podocarpus fleuryi	Species	Podocarpaceae	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
Single protein	1
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT30107	Single protein	Amyloid-beta A4 protein	Homo sapiens	IC50	=	21300.0	nM	PMID[31138471]

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	=	38.5	%	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 NPC600972 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	32472
0.1-0.2	14663
0.2-0.3	1733
0.3-0.4	752
0.4-0.5	177
0.5-0.6	41
0.6-0.7	14
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
0.7164	Intermediate Similarity	NPC111112
0.7083	Intermediate Similarity	NPC290830
0.6849	Remote Similarity	NPC72425
0.6667	Remote Similarity	NPC138299
0.6622	Remote Similarity	NPC303485
0.6557	Remote Similarity	NPC50898
0.6533	Remote Similarity	NPC194593
0.6438	Remote Similarity	NPC259757
0.64	Remote Similarity	NPC71061
0.6364	Remote Similarity	NPC601565
0.6338	Remote Similarity	NPC291746
0.6324	Remote Similarity	NPC183950
0.6212	Remote Similarity	NPC231772
0.6104	Remote Similarity	NPC272064
0.6053	Remote Similarity	NPC603508
0.6026	Remote Similarity	NPC215203
0.597	Remote Similarity	NPC234133
0.5949	Remote Similarity	NPC205026
0.5942	Remote Similarity	NPC12200
0.5844	Remote Similarity	NPC601984
0.5823	Remote Similarity	NPC121649
0.5735	Remote Similarity	NPC62536
0.5735	Remote Similarity	NPC120464
0.5735	Remote Similarity	NPC483773
0.5735	Remote Similarity	NPC601901
0.5714	Remote Similarity	NPC52005
0.5679	Remote Similarity	NPC265624
0.5658	Remote Similarity	NPC603692
0.5641	Remote Similarity	NPC150908
0.5606	Remote Similarity	NPC279121
0.5588	Remote Similarity	NPC241498
0.5556	Remote Similarity	NPC67322
0.5538	Remote Similarity	NPC78540
0.5526	Remote Similarity	NPC183
0.5507	Remote Similarity	NPC198826
0.5507	Remote Similarity	NPC120163
0.5493	Remote Similarity	NPC606638
0.5429	Remote Similarity	NPC78913
0.5375	Remote Similarity	NPC158027
0.5373	Remote Similarity	NPC274121
0.5362	Remote Similarity	NPC301323
0.5362	Remote Similarity	NPC103342
0.5325	Remote Similarity	NPC34089
0.5325	Remote Similarity	NPC196179
0.5325	Remote Similarity	NPC254351
0.5309	Remote Similarity	NPC186227
0.527	Remote Similarity	NPC605634
0.5263	Remote Similarity	NPC112954
0.5256	Remote Similarity	NPC610480
0.5224	Remote Similarity	NPC175013
0.5211	Remote Similarity	NPC600900
0.5176	Remote Similarity	NPC55443
0.5143	Remote Similarity	NPC47815
0.5122	Remote Similarity	NPC159707
0.5072	Remote Similarity	NPC213216
0.5068	Remote Similarity	NPC124784
0.5065	Remote Similarity	NPC288840

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC600972 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6577
0.1-0.2	2520
0.2-0.3	44
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
0.5606	Remote Similarity	NPD1511	Phase 2

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