NPASS Compound

Natural Product: NPC8776

Natural Product ID	NPC8776
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CYCUDJXIJBGDKE-CMKODMSKSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	102194918
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 54 0 0 0 0 0 0 0 0999 V2000 4.2389 -0.1257 2.3259 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0231 -0.7025 0.9541 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3171 -0.5523 0.1833 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9136 -0.0782 0.2175 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6688 -0.6465 0.3476 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6318 -0.0592 -0.3444 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8361 1.0518 -1.1343 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2175 1.7429 -1.9171 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5783 1.1308 -1.7093 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6762 0.5570 -0.3099 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0686 0.3392 0.1392 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4638 1.4076 1.1747 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0326 0.5942 -1.0313 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4117 -0.9845 0.7028 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3128 -1.5207 1.5405 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9374 -1.4373 1.0083 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7643 -0.6268 -0.2511 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8443 -1.5335 -1.4609 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9076 -1.9041 -0.2233 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1124 1.6142 -1.2523 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1542 1.0263 -0.5584 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4129 1.6144 -0.6996 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2704 -0.4080 2.6402 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5109 -0.5424 3.0190 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2274 0.9754 2.2548 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8289 -1.8025 0.9991 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1805 -0.5753 -0.9088 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9825 -1.4414 0.4011 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9193 0.3172 0.5149 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4560 -1.5056 0.9402 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2527 2.7877 -1.5787 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0382 1.7398 -2.9897 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3359 1.9403 -1.8675 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7508 0.3960 -2.5052 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1994 1.3415 0.3524 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4985 1.2623 1.5245 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2892 2.3823 0.6934 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7236 1.2749 2.0107 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6976 0.1245 -1.9522 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2263 1.6925 -1.1388 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0094 0.1541 -0.7277 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3006 -0.8348 1.3939 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5831 -2.5848 1.7864 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3764 -0.9924 2.5369 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5448 -2.4603 0.8201 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2795 -1.0289 1.8323 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8212 -1.5584 -1.9497 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5705 -2.5619 -1.0999 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0877 -1.2922 -2.2435 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6800 -2.8253 -0.0230 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2764 2.4917 -1.8754 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4427 2.6273 -0.5619 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 11 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 6 14 19 1 0 7 20 1 0 20 21 2 0 21 22 1 0 21 4 1 0 17 6 1 0 17 10 1 0 1 23 1 0 1 24 1 0 1 25 1 0 2 26 1 0 3 27 1 0 3 28 1 0 3 29 1 0 5 30 1 0 8 31 1 0 8 32 1 0 9 33 1 0 9 34 1 0 10 35 1 1 12 36 1 0 12 37 1 0 12 38 1 0 13 39 1 0 13 40 1 0 13 41 1 0 14 42 1 1 15 43 1 0 15 44 1 0 16 45 1 0 16 46 1 0 18 47 1 0 18 48 1 0 18 49 1 0 19 50 1 0 20 51 1 0 22 52 1 0 M END

Standard InCHIKey	CYCUDJXIJBGDKE-CMKODMSKSA-N
Standard InCHI	InChI=1S/C20H30O2/c1-12(2)14-11-15-13(10-16(14)21)6-7-17-19(3,4)18(22)8-9-20(15,17)5/h10-12,17-18,21-22H,6-9H2,1-5H3/t17-,18-,20+/m0/s1
SMILES	CC(C)c1cc2c(CC[C@H]3C(C)(C)[C@H](CC[C@]23C)O)cc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.22	Volume:	338.478 ? Van der Waals volume.
Dense:	0.893	LogP:	3.968 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.604 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.02 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	16.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.801	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.585	Fsp³:	0.7
MCE-18:	76.353 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.296	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.108 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.448	Promiscuous compounds:	0.039

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.625	MDCK Permeability:	-4.61
Pgp-inhibitor:	0.665	Pgp-substrate:	0.262
PAMPA:	0.077 ? 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%):	0.766	30% Bioavailability (F30%):	0.705
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.029	MRP1:	0.788
Plasma Protein Binding (PPB):	92.749%	Volume Distribution (VD):	0.078
Fu:	10.149% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.785
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.573	CYP1A2-substrate:	0.367
CYP2C19-inhibitor:	0.996	CYP2C19-substrate:	0.349
CYP2C9-inhibitor:	0.877	CYP2C9-substrate:	0.339
CYP2D6-inhibitor:	0.897	CYP2D6-substrate:	0.374
CYP3A4-inhibitor:	0.992	CYP3A4-substrate:	0.068
CYP2B6-substrate:	0.013	CYP2C8-inhibitor:	0.908
HLM stability:	0.955 ? 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):

9.73

Half-life (T1/2):

1.591

ADMET: Toxicity

hERG Blockers:	0.046	hERG Blockers (10um):	0.358
Human Hepatotoxicity (H-HT):	0.551	Drug-induced Liver Injury (DILI):	0.05
AMES Toxicity:	0.369	Rat Oral Acute Toxicity:	0.424
Maximum Recommended Daily Dose:	0.725	Skin Sensitization:	0.781
Carcinogencity:	0.68	Eye Corrosion:	0.019
Eye Irritation:	0.915	Respiratory Toxicity:	0.799
Drug-induced Neurotoxicity:	0.045	Ototoxicity:	0.72
Hematotoxicity:	0.261	Drug-induced Nephrotoxicity:	0.728
Genotoxicity:	0.131	RPMI-8226 Immunitoxicity:	0.077
A549 Cytotoxicity:	0.148	Hek293 Cytotoxicity:	0.359
BCF:	1.976 ? 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:	4.242 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.489 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.005 ? 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
NPO19645	Chironia krebsii	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/0031-9422(91)80080-K]
NPO16538	Stylophorum diphyllum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22029392]
NPO18135	Clausena vestita	Species	Rutaceae	Eukaryota	whole plants	Yunnan Province, China	2008-JAN	PMID[22093759]
NPO12583	Sauromatum giganteum	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28394604]
NPO16703	Isodon lophanthoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16538	Stylophorum diphyllum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18319	Fraxinus japonica	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16538	Stylophorum diphyllum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18319	Fraxinus japonica	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16703	Isodon lophanthoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12583	Sauromatum giganteum	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO16354	Allium scorodoprasum	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12583	Sauromatum giganteum	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16538	Stylophorum diphyllum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18319	Fraxinus japonica	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18135	Clausena vestita	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16771	Amomum mindanaense	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6896	Haliclona fulva	Species	Chalinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16703	Isodon lophanthoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17735	Acinetobacter genospecies	Species	Moraxellaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO19645	Chironia krebsii	Species	Gentianaceae	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
Activity	6
Inhibition	2

Activity Type	# Activity
Cell line	8

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
NPT113	Cell line	RAW264.7	Mus musculus	Activity	n.a.	n.a.	n.a.	PMID[37146221]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	n.a.	n.a.	%	PMID[37146221]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	91.0	%	PMID[37146221]

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 NPC8776 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	21677
0.1-0.2	27199
0.2-0.3	825
0.3-0.4	100
0.4-0.5	36
0.5-0.6	9
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC308311
0.7	Intermediate Similarity	NPC324602
0.6731	Remote Similarity	NPC477137
0.6538	Remote Similarity	NPC176279
0.6481	Remote Similarity	NPC147179
0.6481	Remote Similarity	NPC606176
0.6481	Remote Similarity	NPC606869
0.6429	Remote Similarity	NPC600507
0.6296	Remote Similarity	NPC601694
0.6226	Remote Similarity	NPC27252
0.6226	Remote Similarity	NPC472979
0.5965	Remote Similarity	NPC36765
0.5614	Remote Similarity	NPC219112
0.5357	Remote Similarity	NPC260323
0.5345	Remote Similarity	NPC192948
0.5345	Remote Similarity	NPC35797
0.5172	Remote Similarity	NPC150601
0.5161	Remote Similarity	NPC481087
0.5085	Remote Similarity	NPC11250
0.5079	Remote Similarity	NPC481011

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC8776 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5993
0.1-0.2	3115
0.2-0.3	39
0.3-0.4	3
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