NPASS Compound

Natural Product: NPC120539

Natural Product ID	NPC120539
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(1S,4S,5As,5Br,7As,11As,11Br,13As,13Br)-4-Hydroxy-5B,8,8,11A,13A-Pentamethyl-1,4,5,5A,6,7,7A,9,10,11,11B,12,13,13B-Tetradecahydrophenanthro[1,2-G][2]Benzofuran-1-Yl] Acetate
IUPAC Name	[(1S,4S,5aS,5bR,7aS,11aS,11bR,13aS,13bR)-4-hydroxy-5b,8,8,11a,13a-pentamethyl-1,4,5,5a,6,7,7a,9,10,11,11b,12,13,13b-tetradecahydrophenanthro[1,2-g][2]benzofuran-1-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL572476
PubChem CID	25158708
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001552] Sesterterpenoids [CHEMONTID:0002883] Scalarane sesterterpenoids

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 73 77 0 0 0 0 0 0 0 0999 V2000 4.6076 -3.2196 -3.1606 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6067 -2.0609 -2.2373 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8177 -0.9171 -2.7087 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3866 -2.1629 -0.8818 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3907 -1.0236 -0.0071 C 0 0 2 0 0 0 0 0 0 0 0 0 5.3431 -1.2074 1.0291 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7555 -0.9563 2.2607 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4575 -0.8292 2.1785 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1043 -1.0106 0.7405 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2386 0.2225 0.3937 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1217 1.4063 0.6391 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9099 0.1100 -1.0434 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5663 0.5585 -1.4743 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5122 0.1685 -0.4693 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1838 0.8389 0.8060 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0682 0.1206 1.3269 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3892 0.4302 2.7329 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4356 -0.5608 3.2122 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0285 -0.1225 4.3778 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1480 2.2893 0.7268 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2441 0.6802 1.8771 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5577 1.1607 1.2720 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8628 0.2338 0.1324 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8937 0.3041 -0.9967 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0591 1.4829 -1.8999 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1734 -0.9238 -1.8831 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4901 -1.5399 -1.6099 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6218 -0.5777 -1.4186 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3097 0.3464 -0.2660 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1044 -0.1975 0.9347 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7799 1.7433 -0.4908 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6262 -3.6596 -3.2292 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2538 -2.8657 -4.1451 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8832 -3.9913 -2.8247 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5913 -0.1595 -0.6367 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3571 -0.8817 3.1740 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4807 -1.9141 0.5863 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8022 2.0883 1.4171 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2245 2.0045 -0.3134 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1890 1.1350 0.8856 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0562 -0.9406 -1.4360 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6667 0.7099 -1.6325 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2745 0.0175 -2.4244 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5088 1.6342 -1.7463 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3438 -0.9424 -0.3110 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7535 -0.9692 1.3001 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6559 1.4535 2.9758 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4711 0.1928 3.3493 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9331 -1.5321 3.4321 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5482 -0.4024 5.1841 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9177 2.5713 0.0144 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4866 2.5949 1.7631 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7281 2.9523 0.5473 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0043 1.4251 2.6769 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3629 -0.3395 2.2366 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5666 2.2174 1.0291 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3371 0.9907 2.0488 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7597 -0.8091 0.5666 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0161 1.4714 -2.4405 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9193 2.4600 -1.4653 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2713 1.3732 -2.7039 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0952 -0.6896 -2.9512 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3889 -1.7164 -1.6964 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7546 -2.1883 -2.4770 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4932 -2.2259 -0.7251 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8898 -0.0206 -2.3530 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5375 -1.2096 -1.2159 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3798 0.6497 1.6097 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0115 -0.7064 0.5949 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4911 -0.8913 1.5349 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2150 1.7774 -1.5328 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0393 2.5244 -0.3477 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6582 2.0255 0.1619 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 6 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 15 20 1 6 15 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 6 24 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 9 5 1 0 16 10 1 0 29 23 1 0 18 8 1 0 24 14 1 0 1 32 1 0 1 33 1 0 1 34 1 0 5 35 1 6 7 36 1 0 9 37 1 1 11 38 1 0 11 39 1 0 11 40 1 0 12 41 1 0 12 42 1 0 13 43 1 0 13 44 1 0 14 45 1 1 16 46 1 1 17 47 1 0 17 48 1 0 18 49 1 1 19 50 1 0 20 51 1 0 20 52 1 0 20 53 1 0 21 54 1 0 21 55 1 0 22 56 1 0 22 57 1 0 23 58 1 1 25 59 1 0 25 60 1 0 25 61 1 0 26 62 1 0 26 63 1 0 27 64 1 0 27 65 1 0 28 66 1 0 28 67 1 0 30 68 1 0 30 69 1 0 30 70 1 0 31 71 1 0 31 72 1 0 31 73 1 0 M END

Standard InCHIKey	FQJRSISTDYPNPR-ARCYHYOLSA-N
Standard InCHI	InChI=1S/C27H42O4/c1-16(28)31-23-22-17(15-30-23)18(29)14-21-26(5)12-8-19-24(2,3)10-7-11-25(19,4)20(26)9-13-27(21,22)6/h15,18-23,29H,7-14H2,1-6H3/t18-,19-,20+,21-,22+,23-,25-,26+,27-/m0/s1
SMILES	CC(=O)O[C@@H]1OC=C2[C@H]1[C@@]1(C)CC[C@H]3[C@@]([C@@H]1C[C@@H]2O)(C)CC[C@@H]1[C@]3(C)CCCC1(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	430.31	Volume:	462.654 ? Van der Waals volume.
Dense:	0.93	LogP:	4.701 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.22 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.373 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	26.0
TPSA:	55.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.531	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.921	Fsp³:	0.889
MCE-18:	94.706 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.63	Fluc inhibitor:	0.019 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.19	Promiscuous compounds:	0.467

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.056	MDCK Permeability:	-4.868
Pgp-inhibitor:	0.96	Pgp-substrate:	0.001
PAMPA:	0.099 ? 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):	0.0
20% Bioavailability (F20%):	0.048	30% Bioavailability (F30%):	0.057
50% Bioavailability (F50%):	0.748

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.12	MRP1:	0.215
Plasma Protein Binding (PPB):	98.012%	Volume Distribution (VD):	0.108
Fu:	3.273% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.512
BSEP inhibitor:	0.978

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.646	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.49
CYP2D6-inhibitor:	0.044	CYP2D6-substrate:	0.017
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.692
HLM stability:	0.09 ? 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):

9.593

Half-life (T1/2):

0.782

ADMET: Toxicity

hERG Blockers:	0.035	hERG Blockers (10um):	0.263
Human Hepatotoxicity (H-HT):	0.705	Drug-induced Liver Injury (DILI):	0.864
AMES Toxicity:	0.856	Rat Oral Acute Toxicity:	0.677
Maximum Recommended Daily Dose:	0.753	Skin Sensitization:	0.999
Carcinogencity:	0.983	Eye Corrosion:	0.128
Eye Irritation:	0.839	Respiratory Toxicity:	0.879
Drug-induced Neurotoxicity:	0.342	Ototoxicity:	0.284
Hematotoxicity:	0.833	Drug-induced Nephrotoxicity:	0.989
Genotoxicity:	0.873	RPMI-8226 Immunitoxicity:	0.068
A549 Cytotoxicity:	0.727	Hek293 Cytotoxicity:	0.615
BCF:	2.58 ? 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:	5.069 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.672 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.378 ? 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
NPO32965	smenospongia sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15497955]
NPO32965	smenospongia sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[16252912]
NPO32965	smenospongia sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18973387]

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
MIC	6

Activity Type	# Activity
Individual protein	1
Organism	6

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4391	Individual protein	Isocitrate lyase	Magnaporthe oryzae (strain 70-15 / FGSC 8958) (Rice blast fungus)(Pyricularia oryzae)	IC50	>	100.0	ug.mL-1	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	>	100.0	ug.mL-1	PMID[26331426]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	=	12.5	ug.mL-1	DrugMatrix in vivo data: Pathology
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	3.12	ug.mL-1	PMID[27096049]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	100.0	ug.mL-1	PMID[22180047]
NPT766	Organism	Proteus vulgaris	Proteus vulgaris	MIC	>	100.0	ug.mL-1	PubChem BioAssay data set
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100.0	ug.mL-1	PMID[9213587]

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 NPC120539 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	18183
0.1-0.2	26897
0.2-0.3	4418
0.3-0.4	308
0.4-0.5	44
0.5-0.6	5
0.6-0.7	3
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
0.6406	Remote Similarity	NPC97867
0.6	Remote Similarity	NPC288952
0.6	Remote Similarity	NPC12680
0.5606	Remote Similarity	NPC246860
0.5469	Remote Similarity	NPC164750
0.5455	Remote Similarity	NPC163902
0.5246	Remote Similarity	NPC257726
0.5072	Remote Similarity	NPC144069

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC120539 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6701
0.1-0.2	2355
0.2-0.3	94
0.3-0.4	0
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