NPASS Compound

Natural Product: NPC218301

Natural Product ID	NPC218301
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Minabeolide 4
IUPAC Name	(3S,6R)-6-[(1S)-1-[(8S,9S,10R,13S,14S,17R)-10,13-dimethyl-3-oxo-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]ethyl]-3-methyloxan-2-one
Synonyms	Minabeolide 4
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1782228
PubChem CID	21628409
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides and derivatives

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 72 0 0 0 0 0 0 0 0999 V2000 -7.1004 -1.6271 1.8924 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1125 -1.4413 1.1316 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2074 -2.5243 0.8288 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1902 -2.2960 0.0323 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8795 -1.0125 -0.5956 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8313 0.0614 -0.2529 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8573 -0.1324 0.5383 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5884 1.3905 -0.8122 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1887 1.7255 -1.1064 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1127 0.7494 -0.8516 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5512 -0.5242 -0.1432 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4731 -1.5541 -0.1748 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1695 -1.0484 0.3444 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2094 0.2840 -0.1464 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0031 1.2476 -0.0165 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3662 2.5339 -0.3508 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1493 2.3735 -0.0986 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1204 1.0821 0.6998 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3012 0.6421 1.3441 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5158 0.0793 0.7912 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3815 -1.2237 0.0596 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7415 -1.8332 -0.2525 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6848 -0.8410 -0.8400 C 0 0 1 0 0 0 0 0 0 0 0 0 5.0662 0.5076 -0.9845 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1960 1.1849 -2.0602 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3465 0.9978 0.0906 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9622 -0.7869 -0.0449 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7499 1.8051 2.2924 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5132 0.3345 -1.6245 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9717 -1.2108 -2.0926 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3580 -3.5128 1.2477 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5341 -3.1308 -0.1719 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5787 0.6526 0.8048 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1019 2.1741 -0.1923 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1784 1.4206 -1.7810 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9358 2.6403 -0.4755 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1227 2.1611 -2.1559 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7488 0.3994 -1.8478 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6727 -0.2197 0.9399 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3838 -2.0658 -1.1549 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7892 -2.3708 0.5411 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1189 -1.0972 1.4491 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5994 -1.7999 -0.0132 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2918 1.2204 1.0530 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6810 3.2965 0.4215 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5826 2.9784 -1.3158 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5796 2.2664 -1.1094 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5689 3.2192 0.4408 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4287 1.4100 1.5866 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9623 -0.1171 2.1502 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1983 -0.2072 1.6646 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8302 -1.9292 0.7576 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8149 -1.2194 -0.8603 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6438 -2.7323 -0.8787 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1446 -2.1732 0.7244 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9513 -1.1874 -1.8765 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1818 0.2073 0.3727 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9607 -1.5150 0.8070 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8591 -1.0711 -0.6687 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4593 1.3462 2.9858 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1227 2.6401 1.7006 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8560 2.1148 2.8662 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5650 0.4084 -1.8932 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0427 1.2287 -2.1377 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0933 -0.5555 -2.1162 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5181 -0.4004 -2.6636 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0595 -1.2436 -2.3875 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5419 -2.1797 -2.4209 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 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 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 23 27 1 0 19 28 1 0 14 29 1 6 5 30 1 6 7 2 1 0 15 10 1 0 26 20 1 0 11 5 1 0 18 14 1 0 3 31 1 0 4 32 1 0 7 33 1 0 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 10 38 1 6 11 39 1 1 12 40 1 0 12 41 1 0 13 42 1 0 13 43 1 0 15 44 1 1 16 45 1 0 16 46 1 0 17 47 1 0 17 48 1 0 18 49 1 1 19 50 1 1 20 51 1 1 21 52 1 0 21 53 1 0 22 54 1 0 22 55 1 0 23 56 1 6 27 57 1 0 27 58 1 0 27 59 1 0 28 60 1 0 28 61 1 0 28 62 1 0 29 63 1 0 29 64 1 0 29 65 1 0 30 66 1 0 30 67 1 0 30 68 1 0 M END

Standard InCHIKey	OIROZVSBVQAEPT-HDSKOFFVSA-N
Standard InCHI	InChI=1S/C27H38O3/c1-16-5-10-24(30-25(16)29)17(2)21-8-9-22-20-7-6-18-15-19(28)11-13-26(18,3)23(20)12-14-27(21,22)4/h11,13,15-17,20-24H,5-10,12,14H2,1-4H3/t16-,17-,20-,21+,22-,23-,24+,26-,27+/m0/s1
SMILES	O=C1C=C[C@]2(C(=C1)CC[C@@H]1[C@@H]2CC[C@]2([C@H]1CC[C@@H]2[C@@H]([C@H]1CC[C@@H](C(=O)O1)C)C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	410.28	Volume:	448.591 ? Van der Waals volume.
Dense:	0.915	LogP:	3.614 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.448 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.038 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	28.0
TPSA:	43.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.533	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.682	Fsp³:	0.778
MCE-18:	82.667 ? 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:	0.767	Fluc inhibitor:	0.234 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.082 ? 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:	0.496	Promiscuous compounds:	0.699

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.245	MDCK Permeability:	-5.016
Pgp-inhibitor:	0.477	Pgp-substrate:	0.001
PAMPA:	0.027 ? 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%):	0.049	30% Bioavailability (F30%):	0.52
50% Bioavailability (F50%):	0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.064
Plasma Protein Binding (PPB):	96.56%	Volume Distribution (VD):	0.242
Fu:	3.137% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.048
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.885	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.975	CYP2D6-substrate:	0.084
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

11.942

Half-life (T1/2):

0.89

ADMET: Toxicity

hERG Blockers:	0.122	hERG Blockers (10um):	0.362
Human Hepatotoxicity (H-HT):	0.72	Drug-induced Liver Injury (DILI):	0.731
AMES Toxicity:	0.168	Rat Oral Acute Toxicity:	0.316
Maximum Recommended Daily Dose:	0.923	Skin Sensitization:	0.99
Carcinogencity:	0.961	Eye Corrosion:	0.706
Eye Irritation:	0.994	Respiratory Toxicity:	0.957
Drug-induced Neurotoxicity:	0.385	Ototoxicity:	0.376
Hematotoxicity:	0.469	Drug-induced Nephrotoxicity:	0.726
Genotoxicity:	0.823	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.099	Hek293 Cytotoxicity:	0.677
BCF:	2.027 ? 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:	4.199 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.26 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.017 ? 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
NPO27202	Paraminabea acronocephala	Species	Alcyoniidae	Eukaryota	n.a.	the western coast of Pingtung county, Taiwan, at a depth of 10 m	2009-MAY	PMID[21425785]
NPO27202	Paraminabea acronocephala	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21425785]
NPO27202	Paraminabea acronocephala	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27202	Paraminabea acronocephala	Species	Alcyoniidae	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
Inhibition	2

Activity Type	# Activity
Cell line	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
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	23.2	%	PMID[21425785]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	22.4	%	PMID[21425785]

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 NPC218301 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	21176
0.1-0.2	24891
0.2-0.3	3664
0.3-0.4	95
0.4-0.5	7
0.5-0.6	10
0.6-0.7	12
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
0.7797	Intermediate Similarity	NPC608739
0.7742	Intermediate Similarity	NPC111684
0.7333	Intermediate Similarity	NPC273199
0.6769	Remote Similarity	NPC177141
0.6727	Remote Similarity	NPC92327
0.6562	Remote Similarity	NPC255309
0.6308	Remote Similarity	NPC470923
0.629	Remote Similarity	NPC474463
0.623	Remote Similarity	NPC105197
0.6119	Remote Similarity	NPC164835
0.6119	Remote Similarity	NPC228669
0.6087	Remote Similarity	NPC58052
0.6066	Remote Similarity	NPC176107
0.6029	Remote Similarity	NPC128488
0.6029	Remote Similarity	NPC304968
0.597	Remote Similarity	NPC310981
0.5775	Remote Similarity	NPC601481
0.5758	Remote Similarity	NPC190211
0.5714	Remote Similarity	NPC281134
0.5417	Remote Similarity	NPC600537
0.5342	Remote Similarity	NPC96377
0.5246	Remote Similarity	NPC54123
0.5238	Remote Similarity	NPC6434
0.52	Remote Similarity	NPC471398
0.52	Remote Similarity	NPC604986

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC218301 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6912
0.1-0.2	1977
0.2-0.3	215
0.3-0.4	44
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