NPASS Compound

Natural Product: NPC118080

Natural Product ID	NPC118080
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ABMRCUKAZOLQBK-PRCHNWEUSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1796004
PubChem CID	56666985
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0002051] Agarofurans

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 68 71 0 0 0 0 0 0 0 0999 V2000 -4.2878 1.8599 -0.9557 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2500 1.5832 0.1076 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6121 2.8264 0.6321 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3823 3.2433 -0.0752 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4308 2.0289 -0.0722 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0029 0.9288 -0.9031 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3461 1.5148 -2.2723 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0762 -0.1921 -1.0878 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6599 -1.5923 -1.0614 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9623 -1.7421 -0.3800 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8499 -0.6314 -0.9725 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2890 0.5078 -0.1856 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8469 -0.0047 1.0471 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9999 -1.3556 1.0594 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3084 -1.8362 1.6615 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8910 -1.9614 1.8813 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1779 -0.8981 -0.7951 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2705 -2.4741 -0.4646 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8268 -3.5667 -1.1067 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4982 -3.8090 -2.2958 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8043 -4.4872 -0.4692 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0907 -0.2158 -0.2924 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3805 -0.2842 -0.8412 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4655 -0.3170 -2.0914 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5870 -0.3194 -0.0348 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5584 -0.2940 1.3400 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7267 -0.3283 2.0907 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9639 -0.3893 1.4812 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9946 -0.4148 0.1085 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8315 -0.3804 -0.6265 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8653 2.4413 -0.3187 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7904 2.5337 0.7049 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3978 2.2242 1.8414 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1949 2.9767 0.5095 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3441 1.8184 -0.5537 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1816 2.9512 -1.2307 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2753 1.1887 -1.8091 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8623 1.2034 0.9915 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3428 2.6937 1.7219 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4050 3.6191 0.6502 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5964 3.6459 -1.0448 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8594 4.0129 0.5269 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4963 1.7135 0.9927 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4282 2.1057 -2.5607 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4597 0.7408 -3.0333 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1822 2.1874 -2.2939 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3466 -0.1408 -2.1523 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8081 -1.9879 -2.1035 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3778 -2.7265 -0.5997 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6248 -0.6175 -2.0530 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8526 -0.9812 2.0920 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9023 -2.4478 0.9508 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1374 -2.5308 2.5375 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6950 -3.0310 1.6106 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0125 -1.3607 1.9494 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2845 -2.0178 2.9396 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6496 -0.4305 -0.0956 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2305 -5.2992 0.0613 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3830 -3.9831 0.3481 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4455 -4.9521 -1.2193 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6023 -0.2468 1.8157 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6839 -0.3071 3.1900 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8731 -0.4157 2.0827 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9455 -0.4622 -0.3846 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8393 -0.4002 -1.7266 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4972 2.5901 -0.5010 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8490 2.6105 1.2996 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1834 4.0829 0.4387 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 6 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 13 14 1 0 14 15 1 0 14 16 1 0 11 17 1 0 9 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 8 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 5 31 1 0 31 32 1 0 32 33 2 0 32 34 1 0 12 2 1 0 30 25 1 0 12 6 1 0 14 10 1 0 1 35 1 0 1 36 1 0 1 37 1 0 2 38 1 1 3 39 1 0 3 40 1 0 4 41 1 0 4 42 1 0 5 43 1 1 7 44 1 0 7 45 1 0 7 46 1 0 8 47 1 6 9 48 1 6 10 49 1 1 11 50 1 6 15 51 1 0 15 52 1 0 15 53 1 0 16 54 1 0 16 55 1 0 16 56 1 0 17 57 1 0 21 58 1 0 21 59 1 0 21 60 1 0 26 61 1 0 27 62 1 0 28 63 1 0 29 64 1 0 30 65 1 0 34 66 1 0 34 67 1 0 34 68 1 0 M END

Standard InCHIKey	ABMRCUKAZOLQBK-PRCHNWEUSA-N
Standard InCHI	InChI=1S/C26H34O8/c1-14-12-13-18(31-15(2)27)25(6)22(33-23(30)17-10-8-7-9-11-17)20(32-16(3)28)19-21(29)26(14,25)34-24(19,4)5/h7-11,14,18-22,29H,12-13H2,1-6H3/t14-,18+,19-,20+,21-,22+,25+,26-/m1/s1
SMILES	C[C@@H]1CC[C@@H]([C@@]2(C)[C@H]([C@H]([C@@H]3[C@H]([C@]12OC3(C)C)O)OC(=O)C)OC(=O)c1ccccc1)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	474.23	Volume:	478.529 ? Van der Waals volume.
Dense:	0.991	LogP:	2.399 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.489 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.066 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	23.0
TPSA:	108.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.524	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.608	Fsp³:	0.654
MCE-18:	139.86 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.402	Fluc inhibitor:	0.043 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.008 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.094	Promiscuous compounds:	0.135

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.224	MDCK Permeability:	-4.888
Pgp-inhibitor:	1.0	Pgp-substrate:	0.288
PAMPA:	0.184 ? 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%):	0.462	30% Bioavailability (F30%):	0.839
50% Bioavailability (F50%):	0.945

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.05	MRP1:	0.999
Plasma Protein Binding (PPB):	78.562%	Volume Distribution (VD):	-0.403
Fu:	19.501% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.666	BCRP inhibitor:	0.067
BSEP inhibitor:	0.988

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.402
CYP2C19-inhibitor:	0.148	CYP2C19-substrate:	0.077
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.558
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.076
CYP3A4-inhibitor:	0.135	CYP3A4-substrate:	0.629
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.963 ? 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):

7.581

Half-life (T1/2):

0.687

ADMET: Toxicity

hERG Blockers:	0.027	hERG Blockers (10um):	0.29
Human Hepatotoxicity (H-HT):	0.237	Drug-induced Liver Injury (DILI):	0.439
AMES Toxicity:	0.344	Rat Oral Acute Toxicity:	0.417
Maximum Recommended Daily Dose:	0.446	Skin Sensitization:	0.95
Carcinogencity:	0.6	Eye Corrosion:	0.038
Eye Irritation:	0.582	Respiratory Toxicity:	0.151
Drug-induced Neurotoxicity:	0.106	Ototoxicity:	0.367
Hematotoxicity:	0.094	Drug-induced Nephrotoxicity:	0.564
Genotoxicity:	0.73	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.057	Hek293 Cytotoxicity:	0.135
BCF:	0.549 ? 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:	3.378 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.946 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.36 ? 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
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18616221]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	stems	Montecristo National Park, province of Santa Ana, El Salvador	2004-JUN	PMID[20873773]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21419633]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25695368]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	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
MIC	2

Activity Type	# Activity
Organism	2

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
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	>	25.0	ug.mL-1	Open TG-GATES in vivo data: Biochemistry
NPT790	Organism	Mycobacterium tuberculosis H37Rv	Mycobacterium tuberculosis H37Rv	MIC	>	25.0	ug.mL-1	PMID[22239408]

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 NPC118080 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	9085
0.1-0.2	36914
0.2-0.3	3176
0.3-0.4	537
0.4-0.5	102
0.5-0.6	27
0.6-0.7	7
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8305	Intermediate Similarity	NPC301556
0.806	Intermediate Similarity	NPC29704
0.806	Intermediate Similarity	NPC470157
0.7812	Intermediate Similarity	NPC483846
0.7231	Intermediate Similarity	NPC87448
0.7143	Intermediate Similarity	NPC100913
0.6769	Remote Similarity	NPC483863
0.6269	Remote Similarity	NPC66761
0.6269	Remote Similarity	NPC483843
0.6216	Remote Similarity	NPC470153
0.6087	Remote Similarity	NPC483847
0.6087	Remote Similarity	NPC470152
0.6029	Remote Similarity	NPC211137
0.5974	Remote Similarity	NPC70403
0.5974	Remote Similarity	NPC177940
0.5797	Remote Similarity	NPC476094
0.5694	Remote Similarity	NPC163719
0.5694	Remote Similarity	NPC95810
0.5634	Remote Similarity	NPC97947
0.5634	Remote Similarity	NPC475759
0.5571	Remote Similarity	NPC475429
0.5362	Remote Similarity	NPC147561
0.5286	Remote Similarity	NPC283375
0.5286	Remote Similarity	NPC474608
0.527	Remote Similarity	NPC291599
0.527	Remote Similarity	NPC90257
0.527	Remote Similarity	NPC200471
0.527	Remote Similarity	NPC69357
0.527	Remote Similarity	NPC472575
0.5263	Remote Similarity	NPC306146
0.5263	Remote Similarity	NPC483841
0.5256	Remote Similarity	NPC481490
0.525	Remote Similarity	NPC470159
0.525	Remote Similarity	NPC4421
0.5135	Remote Similarity	NPC163087
0.5135	Remote Similarity	NPC470158
0.5132	Remote Similarity	NPC473758
0.507	Remote Similarity	NPC183122
0.5067	Remote Similarity	NPC483845
0.5062	Remote Similarity	NPC472571

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC118080 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2783
0.1-0.2	6072
0.2-0.3	293
0.3-0.4	2
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