NPASS Compound

Natural Product: NPC21064

Natural Product ID	NPC21064
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4'-O-Acetyl-3Beta-Pregna-5,20-Dienyl-Beta-D-Arabinopyranoside
IUPAC Name	[(3R,4S,5S,6S)-6-[[(3S,8S,9S,10R,13R,14S,17R)-17-ethenyl-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-dihydroxyoxan-3-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL463005
PubChem CID	16091487
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001013] Steroidal glycosides

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 76 80 0 0 0 0 0 0 0 0999 V2000 -8.4045 0.6127 -0.2788 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3841 -0.1195 -0.6726 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3648 -0.5498 0.3030 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2629 -2.0773 0.1811 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8021 -2.3715 -0.1027 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1268 -1.1771 0.4656 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9857 -0.0443 -0.0441 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9027 0.1406 -1.5280 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5973 1.1987 0.6711 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1472 1.4983 0.3971 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2458 0.3295 0.6907 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7246 -0.9444 0.0091 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8709 -2.0929 0.4344 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5218 -1.7108 0.9094 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0029 -0.4951 0.8381 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8519 0.5926 0.2235 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7532 0.5094 -1.2689 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3105 1.8868 0.7872 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1137 2.1185 0.4087 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0169 0.9624 0.6818 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3659 -0.2105 1.3463 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6178 0.4875 -0.5042 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9950 0.6339 -0.3651 C 0 0 2 0 0 0 0 0 0 0 0 0 4.4165 1.5208 -1.3556 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7625 1.8594 -1.1986 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6229 0.6182 -1.2333 C 0 0 2 0 0 0 0 0 0 0 0 0 5.7411 -0.5760 -1.5881 C 0 0 2 0 0 0 0 0 0 0 0 0 4.7023 -0.7041 -0.4938 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7893 -1.7237 -0.7811 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5323 -1.7243 -1.6629 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1978 0.3246 0.0191 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5733 0.1751 0.0956 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2820 0.3055 -0.9592 O 0 0 0 0 0 0 0 0 0 0 0 0 9.3075 -0.1329 1.3394 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5300 0.9218 0.7660 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1898 0.9623 -0.9480 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2926 -0.4038 -1.7018 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6734 -0.2593 1.3158 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5002 -2.5083 1.1957 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9431 -2.4830 -0.5650 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4909 -3.2598 0.4896 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5960 -2.5234 -1.1754 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1834 -1.1873 1.5612 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9631 0.6086 -1.8563 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7114 0.8819 -1.7952 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0646 -0.7719 -2.1093 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1893 2.0473 0.2243 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8193 1.1964 1.7469 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9915 1.9141 -0.6229 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8507 2.3159 1.0958 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2337 0.1303 1.7657 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6828 -0.8573 -1.0922 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3455 -2.6581 1.2903 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7445 -2.7837 -0.4179 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1144 -2.4777 1.3589 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7075 -0.5865 -1.5258 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5950 0.9834 -1.7997 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1703 0.9549 -1.6781 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3783 1.8287 1.8849 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8995 2.7648 0.4505 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2025 2.4022 -0.6799 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4401 3.0555 0.9463 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8047 1.3258 1.4055 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2664 0.0021 2.4517 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9620 -1.1241 1.1802 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2627 1.0740 0.6195 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9415 2.4747 -0.3017 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0383 2.4766 -2.0783 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4092 0.6913 -2.0265 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2077 -0.3864 -2.5324 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2401 -0.9583 0.4384 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2488 -2.5814 -0.5431 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9588 -1.7234 -2.5567 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0940 0.6629 1.4580 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8118 -1.1173 1.1823 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6258 -0.1450 2.2128 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 6 7 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 2 0 15 16 1 0 16 17 1 6 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 27 30 1 0 26 31 1 0 31 32 1 0 32 33 2 0 32 34 1 0 7 3 1 0 16 11 1 0 28 23 1 0 12 6 1 0 21 15 1 0 1 35 1 0 1 36 1 0 2 37 1 0 3 38 1 1 4 39 1 0 4 40 1 0 5 41 1 0 5 42 1 0 6 43 1 1 8 44 1 0 8 45 1 0 8 46 1 0 9 47 1 0 9 48 1 0 10 49 1 0 10 50 1 0 11 51 1 1 12 52 1 6 13 53 1 0 13 54 1 0 14 55 1 0 17 56 1 0 17 57 1 0 17 58 1 0 18 59 1 0 18 60 1 0 19 61 1 0 19 62 1 0 20 63 1 1 21 64 1 0 21 65 1 0 23 66 1 1 25 67 1 0 25 68 1 0 26 69 1 6 27 70 1 6 28 71 1 1 29 72 1 0 30 73 1 0 34 74 1 0 34 75 1 0 34 76 1 0 M END

Standard InCHIKey	LYCUXBSMEHKLCL-GESZSZFKSA-N
Standard InCHI	InChI=1S/C28H42O6/c1-5-17-7-9-21-20-8-6-18-14-19(10-12-28(18,4)22(20)11-13-27(17,21)3)34-26-25(31)24(30)23(15-32-26)33-16(2)29/h5-6,17,19-26,30-31H,1,7-15H2,2-4H3/t17-,19-,20-,21-,22-,23+,24+,25-,26-,27+,28-/m0/s1
SMILES	C=C[C@H]1CC[C@@H]2[C@]1(C)CC[C@H]1[C@H]2CC=C2[C@]1(C)CC[C@@H](C2)O[C@@H]1OC[C@H]([C@H]([C@@H]1O)O)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	474.3	Volume:	494.894 ? Van der Waals volume.
Dense:	0.958	LogP:	5.377 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.492 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.38 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	28.0
TPSA:	85.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.47	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.871	Fsp³:	0.821
MCE-18:	89.098 ? 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:	0.891	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? 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:	0.268	Promiscuous compounds:	0.097

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.379	MDCK Permeability:	-4.965
Pgp-inhibitor:	0.187	Pgp-substrate:	0.042
PAMPA:	0.079 ? 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%):	0.068	30% Bioavailability (F30%):	0.778
50% Bioavailability (F50%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.145	MRP1:	0.026
Plasma Protein Binding (PPB):	83.604%	Volume Distribution (VD):	-0.071
Fu:	16.23% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.963
BSEP inhibitor:	0.792

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.13
CYP2C19-inhibitor:	0.906	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.068
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.181
CYP3A4-inhibitor:	0.987	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.995 ? 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):

9.022

Half-life (T1/2):

1.094

ADMET: Toxicity

hERG Blockers:	0.086	hERG Blockers (10um):	0.349
Human Hepatotoxicity (H-HT):	0.299	Drug-induced Liver Injury (DILI):	0.744
AMES Toxicity:	0.5	Rat Oral Acute Toxicity:	0.143
Maximum Recommended Daily Dose:	0.61	Skin Sensitization:	0.989
Carcinogencity:	0.826	Eye Corrosion:	0.034
Eye Irritation:	0.718	Respiratory Toxicity:	0.619
Drug-induced Neurotoxicity:	0.046	Ototoxicity:	0.583
Hematotoxicity:	0.444	Drug-induced Nephrotoxicity:	0.34
Genotoxicity:	0.262	RPMI-8226 Immunitoxicity:	0.04
A549 Cytotoxicity:	0.537	Hek293 Cytotoxicity:	0.853
BCF:	2.137 ? 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:	4.075 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.152 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.855 ? 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
NPO28209	Muricea austera	Species	Plexauridae	Eukaryota	n.a.	Pacific coast of Panama	n.a.	PMID[17067146]
NPO28209	Muricea austera	Species	Plexauridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28209	Muricea austera	Species	Plexauridae	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
IC50	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
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	80000.0	nM	PMID[19459643]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	101000.0	nM	DOI[10.6019/CHEMBL1201861]

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 NPC21064 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	16612
0.1-0.2	23530
0.2-0.3	8850
0.3-0.4	715
0.4-0.5	134
0.5-0.6	13
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	Natural Product ID
0.7246	Intermediate Similarity	NPC207617
0.7246	Intermediate Similarity	NPC607440
0.7083	Intermediate Similarity	NPC154452
0.7083	Intermediate Similarity	NPC121072
0.5814	Remote Similarity	NPC295389
0.5696	Remote Similarity	NPC22140
0.5696	Remote Similarity	NPC243728
0.5696	Remote Similarity	NPC158088
0.5417	Remote Similarity	NPC153987
0.5342	Remote Similarity	NPC44083
0.5287	Remote Similarity	NPC486114
0.5281	Remote Similarity	NPC272015
0.5233	Remote Similarity	NPC62188
0.5181	Remote Similarity	NPC282669
0.5128	Remote Similarity	NPC278939
0.5114	Remote Similarity	NPC220048
0.5053	Remote Similarity	NPC295980

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC21064 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6032
0.1-0.2	2836
0.2-0.3	256
0.3-0.4	21
0.4-0.5	5
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