NPASS Compound

Natural Product: NPC481208

Natural Product ID	NPC481208
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GJDPEKDRWHGCCN-CFYFKYHRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
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 75 80 0 0 0 0 0 0 0 0999 V2000 7.8310 -1.1713 1.4019 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3397 -0.4296 0.1699 C 0 0 2 0 0 0 0 0 0 0 0 0 6.2432 0.4871 0.5943 C 0 0 1 0 0 0 0 0 0 0 0 0 6.3124 1.8316 -0.0080 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3399 2.5399 -0.0752 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9837 2.1557 -0.4928 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2301 1.0610 -0.5372 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8092 0.8632 -0.9572 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0575 2.1876 -0.7983 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6346 2.0107 -1.2087 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0016 0.9450 -0.3593 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4256 0.6781 -0.7891 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0630 -0.1177 0.3115 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3811 -1.4694 0.3530 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1065 -1.3671 0.4750 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7360 -0.3689 -0.4354 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7091 -0.9217 -1.8401 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1617 -0.1152 -0.0013 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9755 -1.3621 0.1147 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2589 -0.9840 0.8679 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0355 -0.0922 -0.0711 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6103 -0.8659 -1.1924 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1177 -1.0376 -2.3517 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8106 -1.3718 -0.7150 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4129 -0.3024 0.1726 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0391 0.2009 1.3174 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0200 1.2549 0.8489 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7594 0.6388 -0.3459 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2521 -0.7225 0.0948 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.0668 -0.8731 1.6001 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5464 -2.2766 1.9823 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7533 -0.7805 1.9885 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5929 -0.8939 -0.2008 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7619 1.4570 -0.7903 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5165 1.7960 -2.1173 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0995 -1.0687 2.2411 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9519 -2.2599 1.1964 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8101 -0.7592 1.7183 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1793 0.0854 -0.3204 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1113 0.5207 1.6963 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7084 3.1811 -0.7661 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7221 0.5710 -2.0097 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5037 2.9652 -1.4723 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1100 2.5436 0.2368 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5085 1.8429 -2.2824 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0987 2.9692 -0.9639 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0039 1.2997 0.6863 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3944 0.0610 -1.7010 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9713 1.6104 -1.0267 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7973 0.3813 1.2887 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6809 -2.0999 -0.5243 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7647 -1.9973 1.2518 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5201 -2.3861 0.2190 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3563 -1.1945 1.5345 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0614 -1.8138 -1.9214 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4237 -0.1709 -2.5966 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7445 -1.2698 -2.1006 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1175 0.3852 0.9838 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4896 -2.1449 0.6927 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3266 -1.7042 -0.8884 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8674 -1.8663 1.0839 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0060 -0.4030 1.7750 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3006 0.6160 2.0382 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4848 2.1779 0.5403 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7398 1.5545 1.6247 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0320 0.4694 -1.1532 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6829 -1.5535 -0.3722 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7443 -0.1533 2.1091 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6722 -2.9704 1.8197 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8062 -2.2890 3.0425 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3346 -2.6306 1.3006 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7629 -0.7469 -1.1641 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5372 2.3191 -2.1394 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3072 2.4535 -2.5362 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4210 0.8910 -2.7684 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 2 0 4 6 1 0 6 7 2 0 7 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 6 16 18 1 0 18 19 1 0 19 20 1 0 21 20 1 1 21 22 1 0 22 23 2 0 22 24 1 0 13 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 30 32 1 0 29 33 1 0 28 34 1 0 34 35 1 0 24 2 1 0 32 26 1 0 21 3 1 0 21 7 1 0 18 8 1 0 16 11 1 0 1 36 1 0 1 37 1 0 1 38 1 0 2 39 1 6 3 40 1 1 6 41 1 0 8 42 1 6 9 43 1 0 9 44 1 0 10 45 1 0 10 46 1 0 11 47 1 1 12 48 1 0 12 49 1 0 13 50 1 1 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 17 55 1 0 17 56 1 0 17 57 1 0 18 58 1 1 19 59 1 0 19 60 1 0 20 61 1 0 20 62 1 0 26 63 1 1 27 64 1 0 27 65 1 0 28 66 1 6 29 67 1 6 30 68 1 1 31 69 1 0 31 70 1 0 31 71 1 0 33 72 1 0 35 73 1 0 35 74 1 0 35 75 1 0 M END

Standard InCHIKey	GJDPEKDRWHGCCN-CFYFKYHRSA-N
Standard InCHI	InChI=1S/C28H40O7/c1-14-24-21(29)12-20-18-6-5-16-11-17(35-23-13-22(32-4)25(30)15(2)33-23)7-9-27(16,3)19(18)8-10-28(20,24)26(31)34-14/h12,14-19,22-25,30H,5-11,13H2,1-4H3/t14-,15-,16+,17+,18-,19+,22+,23+,24+,25-,27+,28-/m1/s1
SMILES	C[C@@H]1[C@H]2C(=O)C=C3[C@@H]4CC[C@H]5C[C@H](CC[C@]5(C)[C@H]4CC[C@]23C(=O)O1)O[C@H]1C[C@@H]([C@@H]([C@@H](C)O1)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	488.28	Volume:	495.128 ? Van der Waals volume.
Dense:	0.986	LogP:	3.658 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.559 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.238 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	32.0
TPSA:	91.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.48	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.635	Fsp³:	0.857
MCE-18:	139.462 ? 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:	0.828	Fluc inhibitor:	0.007 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.087 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.204	Promiscuous compounds:	0.671

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.294	MDCK Permeability:	-5.096
Pgp-inhibitor:	0.294	Pgp-substrate:	0.608
PAMPA:	0.686 ? 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%):	0.329	30% Bioavailability (F30%):	0.317
50% Bioavailability (F50%):	0.897

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012	MRP1:	0.779
Plasma Protein Binding (PPB):	65.968%	Volume Distribution (VD):	0.063
Fu:	35.695% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.057
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.696	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.994	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.555
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	0.435
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.372
HLM stability:	0.99 ? 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):

7.876

Half-life (T1/2):

2.003

ADMET: Toxicity

hERG Blockers:	0.053	hERG Blockers (10um):	0.258
Human Hepatotoxicity (H-HT):	0.541	Drug-induced Liver Injury (DILI):	0.99
AMES Toxicity:	0.917	Rat Oral Acute Toxicity:	0.44
Maximum Recommended Daily Dose:	0.462	Skin Sensitization:	0.997
Carcinogencity:	0.827	Eye Corrosion:	0.004
Eye Irritation:	0.213	Respiratory Toxicity:	0.326
Drug-induced Neurotoxicity:	0.183	Ototoxicity:	0.827
Hematotoxicity:	0.652	Drug-induced Nephrotoxicity:	0.977
Genotoxicity:	0.8	RPMI-8226 Immunitoxicity:	0.188
A549 Cytotoxicity:	0.804	Hek293 Cytotoxicity:	0.579
BCF:	1.973 ? 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:	4.281 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.638 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.202 ? 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
NPO40068	Chonemorpha megacalyx	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31148449]

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	4

Activity Type	# Activity
Cell line	4

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
NPT306	Cell line	PC-3	Homo sapiens	IC50	>	50000.0	nM	PMID[31148449]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	50000.0	nM	PMID[31148449]
NPT81	Cell line	A549	Homo sapiens	IC50	>	50000.0	nM	PMID[31148449]
NPT1374	Cell line	WI-38	Homo sapiens	IC50	>	50000.0	nM	PMID[31148449]

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 NPC481208 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	18609
0.1-0.2	26844
0.2-0.3	4220
0.3-0.4	140
0.4-0.5	28
0.5-0.6	12
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8947	High Similarity	NPC481207
0.8831	High Similarity	NPC481206
0.7733	Intermediate Similarity	NPC481205
0.6628	Remote Similarity	NPC481204
0.6552	Remote Similarity	NPC481203
0.5568	Remote Similarity	NPC477580
0.5529	Remote Similarity	NPC481202
0.5333	Remote Similarity	NPC84949
0.5333	Remote Similarity	NPC480562
0.5333	Remote Similarity	NPC74945
0.5333	Remote Similarity	NPC31354
0.5333	Remote Similarity	NPC69576
0.5222	Remote Similarity	NPC99080
0.5053	Remote Similarity	NPC103534
0.5053	Remote Similarity	NPC44899
0.5053	Remote Similarity	NPC304260
0.5053	Remote Similarity	NPC29639

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC481208 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6798
0.1-0.2	2188
0.2-0.3	153
0.3-0.4	8
0.4-0.5	3
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