NPASS Compound

Natural Product: NPC122859

Natural Product ID	NPC122859
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CSYZCEMSEOUURJ-NQRURKCISA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	53355243
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 69 74 0 0 0 0 0 0 0 0999 V2000 3.8680 -0.3582 2.8281 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4924 -0.1913 1.4794 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8996 0.3643 1.6713 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9454 -0.7210 1.5079 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9893 1.3791 0.6030 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9465 2.1394 0.3720 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8164 1.3689 -0.1364 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7757 0.7802 0.5953 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8189 0.0767 -0.3758 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1924 1.0951 -1.2682 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0796 1.5733 -2.3752 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8473 0.6265 -1.8099 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9602 -0.7880 -2.3594 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1750 -1.5876 -1.7028 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1068 -0.5130 -1.3097 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1527 -0.8663 -0.2906 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8973 -2.1170 -0.6453 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8470 -2.4158 0.5263 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8034 -1.2380 0.4591 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0704 -1.4563 0.2542 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0722 -0.3912 0.1647 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2865 -0.6510 -0.0328 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5811 0.9689 0.3167 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2798 1.1403 0.5273 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2655 0.1076 0.6316 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7964 0.1557 2.1148 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0736 0.3627 -0.2378 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2418 1.5153 0.2449 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0061 1.7652 -0.5373 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1800 0.5193 -0.7064 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5097 0.0888 0.5080 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0304 0.2698 1.6533 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7616 -0.5193 0.3860 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2040 -1.2511 2.8343 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2904 0.4991 3.1815 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7005 -0.6015 3.5515 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6071 -1.1799 0.9775 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0213 0.8457 2.6635 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4480 -1.7034 1.6297 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3705 -0.7055 0.4645 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7569 -0.6324 2.2728 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2371 1.5579 1.1479 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4287 -0.6848 -0.9006 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9551 1.9932 -0.6326 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8677 0.8194 -2.5943 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4938 1.6877 -3.3111 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5259 2.5800 -2.1766 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5258 1.3101 -2.5999 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8896 -1.2870 -2.0933 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8047 -0.8061 -3.4655 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1767 -2.1296 -0.8192 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6305 -2.2501 -2.4801 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6019 -0.0293 -2.1722 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7452 -0.9992 0.7170 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2090 -2.9357 -0.8410 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5417 -1.8885 -1.5233 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3353 -2.3438 1.4812 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3369 -3.3628 0.3535 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4097 -2.5095 0.1410 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2815 1.8147 0.2558 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0138 2.2179 0.6238 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6340 -0.3112 2.7065 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7208 1.1924 2.4676 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9183 -0.4619 2.2816 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3738 0.5622 -1.2791 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8852 2.4395 0.1566 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0456 1.4053 1.3296 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4048 2.5250 -0.0226 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2523 2.1401 -1.5456 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 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 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 19 20 2 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 1 1 25 27 1 0 27 28 1 0 28 29 1 0 30 29 1 1 30 31 1 0 31 32 2 0 31 33 1 0 8 2 1 0 33 9 1 0 30 12 1 0 30 15 1 0 27 16 1 0 25 19 1 0 1 34 1 0 1 35 1 0 1 36 1 0 2 37 1 6 3 38 1 1 4 39 1 0 4 40 1 0 4 41 1 0 8 42 1 1 9 43 1 6 10 44 1 1 11 45 1 0 11 46 1 0 11 47 1 0 12 48 1 6 13 49 1 0 13 50 1 0 14 51 1 0 14 52 1 0 15 53 1 6 16 54 1 1 17 55 1 0 17 56 1 0 18 57 1 0 18 58 1 0 20 59 1 0 23 60 1 0 24 61 1 0 26 62 1 0 26 63 1 0 26 64 1 0 27 65 1 6 28 66 1 0 28 67 1 0 29 68 1 0 29 69 1 0 M END

Standard InCHIKey	CSYZCEMSEOUURJ-NQRURKCISA-N
Standard InCHI	InChI=1S/C28H36O5/c1-14-15(2)25(30)32-23(14)24-16(3)20-7-8-22-19-6-5-17-13-18(29)9-11-27(17,4)21(19)10-12-28(20,22)26(31)33-24/h9,11,13-16,19-24H,5-8,10,12H2,1-4H3/t14-,15-,16+,19-,20-,21+,22+,23-,24+,27+,28+/m1/s1
SMILES	C[C@@H]1[C@@H](C)C(=O)O[C@H]1[C@@H]1[C@@H](C)[C@H]2CC[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4CC[C@]23C(=O)O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	452.26	Volume:	472.274 ? Van der Waals volume.
Dense:	0.958	LogP:	3.594 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.547 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.714 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	33.0
TPSA:	69.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.542	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.611	Fsp³:	0.75
MCE-18:	136.673 ? 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:	0.952	Fluc inhibitor:	0.091 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.085 ? 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:	0.388	Promiscuous compounds:	0.468

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.019	MDCK Permeability:	-4.81
Pgp-inhibitor:	0.978	Pgp-substrate:	0.014
PAMPA:	0.066 ? 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%):	0.648	30% Bioavailability (F30%):	0.781
50% Bioavailability (F50%):	0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.741	MRP1:	0.949
Plasma Protein Binding (PPB):	97.45%	Volume Distribution (VD):	0.024
Fu:	2.646% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.948
OATP1B3 inhibitor:	0.978	BCRP inhibitor:	0.071
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.303	CYP1A2-substrate:	0.008
CYP2C19-inhibitor:	0.026	CYP2C19-substrate:	0.014
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.754
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.552 ? 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):

9.695

Half-life (T1/2):

1.414

ADMET: Toxicity

hERG Blockers:	0.07	hERG Blockers (10um):	0.287
Human Hepatotoxicity (H-HT):	0.742	Drug-induced Liver Injury (DILI):	0.838
AMES Toxicity:	0.355	Rat Oral Acute Toxicity:	0.478
Maximum Recommended Daily Dose:	0.76	Skin Sensitization:	0.993
Carcinogencity:	0.958	Eye Corrosion:	0.141
Eye Irritation:	0.953	Respiratory Toxicity:	0.785
Drug-induced Neurotoxicity:	0.393	Ototoxicity:	0.44
Hematotoxicity:	0.472	Drug-induced Nephrotoxicity:	0.896
Genotoxicity:	0.986	RPMI-8226 Immunitoxicity:	0.09
A549 Cytotoxicity:	0.162	Hek293 Cytotoxicity:	0.572
BCF:	2.036 ? 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:	4.173 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.166 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.969 ? 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

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

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 NPC122859 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	22289
0.1-0.2	25597
0.2-0.3	1898
0.3-0.4	46
0.4-0.5	6
0.5-0.6	18
0.6-0.7	4
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
0.6769	Remote Similarity	NPC164835
0.6769	Remote Similarity	NPC228669
0.6462	Remote Similarity	NPC255309
0.6061	Remote Similarity	NPC608739
0.5915	Remote Similarity	NPC96377
0.5915	Remote Similarity	NPC601481
0.5909	Remote Similarity	NPC218301
0.5763	Remote Similarity	NPC92327
0.5672	Remote Similarity	NPC273199
0.5652	Remote Similarity	NPC310981
0.5556	Remote Similarity	NPC58052
0.5455	Remote Similarity	NPC474463
0.5417	Remote Similarity	NPC111684
0.5385	Remote Similarity	NPC105197
0.5278	Remote Similarity	NPC177141
0.5231	Remote Similarity	NPC176107
0.5205	Remote Similarity	NPC281134
0.5161	Remote Similarity	NPC54123
0.5156	Remote Similarity	NPC6434
0.507	Remote Similarity	NPC470923
0.5068	Remote Similarity	NPC128488
0.5068	Remote Similarity	NPC304968

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC122859 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6967
0.1-0.2	1948
0.2-0.3	193
0.3-0.4	40
0.4-0.5	1
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
0.5156	Remote Similarity	NPD4195	Phase 4

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