NPASS Compound

Natural Product: NPC539394

Natural Product ID	NPC539394
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Convallamarogenin
IUPAC Name	(1~{S},2~{S},4~{S},6~{R},7~{S},8~{R},9~{S},12~{S},13~{S},14~{R},16~{R},18~{R})-7,9,13-trimethyl-5'-methylene-spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2'-tetrahydropyran]-14,16-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 78 0 0 0 0 0 0 0 0999 V2000 7.5965 1.8870 0.3288 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5701 1.0547 0.2274 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0973 0.5692 -1.1078 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5934 0.5032 -1.1038 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0388 -0.1148 0.1445 C 0 0 1 0 0 0 0 0 0 0 0 0 5.0262 -0.5050 1.0455 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8248 0.5503 1.4130 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1702 0.7249 0.8341 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3051 -0.0755 1.5532 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9642 0.6099 1.8030 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0192 -0.2607 1.1112 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2928 0.3779 0.7113 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0623 0.7570 1.9436 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3147 1.4692 1.5110 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6139 1.3124 0.0571 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9865 1.8401 -0.2171 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0824 0.9263 0.2302 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.2853 1.4061 -0.3050 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8993 -0.4744 -0.3140 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5365 -1.0227 -0.0413 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3711 -2.2061 -0.7426 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4202 -0.0912 -0.4559 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4889 -0.0027 -1.9856 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1292 -0.6730 -0.0117 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3815 -1.3146 -1.1454 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0170 -1.7846 -0.7816 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7899 -0.7344 -0.1054 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0368 0.4086 -1.0492 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0142 -1.2145 0.5871 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2250 -1.3355 -0.2571 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9690 -2.6052 0.1739 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1167 2.2350 -0.5511 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9423 2.2408 1.2903 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5275 -0.4150 -1.3716 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4100 1.3042 -1.8647 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2098 1.5560 -1.2156 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2868 -0.0575 -2.0189 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6060 0.1454 2.1126 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2822 1.3815 1.9048 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7561 -0.4344 2.4949 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9771 1.6618 1.4682 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7451 0.5915 2.8951 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2364 -1.1467 1.7368 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0749 1.2419 0.0543 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4639 1.3351 2.6695 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3846 -0.2030 2.4295 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1625 1.1991 2.1712 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1354 2.5689 1.6897 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8961 1.9584 -0.5265 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1421 2.1575 -1.2724 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0920 2.7907 0.3825 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2146 0.8958 1.3189 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7246 2.0472 0.2923 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1528 -0.5461 -1.3911 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6336 -1.1156 0.2165 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3970 -1.2292 1.0376 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9486 -2.8880 -0.3026 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8042 0.7742 -2.3615 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5255 0.3857 -2.1949 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3646 -0.9877 -2.4478 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2954 -1.4843 0.7545 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9764 -2.2110 -1.4516 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3822 -0.6580 -2.0632 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5099 -2.0477 -1.7390 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0727 -2.7381 -0.2147 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7479 0.0917 -1.8159 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3592 1.3355 -0.5140 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0795 0.6650 -1.5399 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7565 -2.1297 1.1561 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0538 -1.4002 -1.3360 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2417 -3.3207 0.6508 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7340 -2.4038 0.9261 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4168 -3.1281 -0.6840 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 1 6 7 1 0 5 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 17 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 22 23 1 6 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 6 27 29 1 0 29 30 1 0 30 31 1 0 7 2 1 0 29 9 1 0 30 5 1 0 27 11 1 0 24 12 1 0 22 15 1 0 1 32 1 0 1 33 1 0 3 34 1 0 3 35 1 0 4 36 1 0 4 37 1 0 7 38 1 0 7 39 1 0 9 40 1 1 10 41 1 0 10 42 1 0 11 43 1 1 12 44 1 6 13 45 1 0 13 46 1 0 14 47 1 0 14 48 1 0 15 49 1 6 16 50 1 0 16 51 1 0 17 52 1 1 18 53 1 0 19 54 1 0 19 55 1 0 20 56 1 1 21 57 1 0 23 58 1 0 23 59 1 0 23 60 1 0 24 61 1 1 25 62 1 0 25 63 1 0 26 64 1 0 26 65 1 0 28 66 1 0 28 67 1 0 28 68 1 0 29 69 1 1 30 70 1 6 31 71 1 0 31 72 1 0 31 73 1 0 M END

Standard InCHIKey	XLHFBXMTUNORSV-ZENYHQJXSA-N
Standard InCHI	InChI=1S/C27H42O4/c1-15-7-10-27(30-14-15)16(2)24-22(31-27)13-21-19-6-5-17-11-18(28)12-23(29)26(17,4)20(19)8-9-25(21,24)3/h16-24,28-29H,1,5-14H2,2-4H3/t16-,17+,18+,19+,20-,21-,22-,23+,24-,25-,26-,27+/m0/s1
SMILES	C=C1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@@H]5C[C@@H](O)C[C@@H](O)[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	430.31	Volume:	456.734 ? Van der Waals volume.
Dense:	0.942	LogP:	4.28 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.947 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.089 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	31.0
TPSA:	58.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.548	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.578	Fsp³:	0.926
MCE-18:	142.308 ? 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:	0.366	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.019 ? 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:	0.185	Promiscuous compounds:	0.443

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.197	MDCK Permeability:	-5.015
Pgp-inhibitor:	0.171	Pgp-substrate:	0.231
PAMPA:	0.329 ? 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%):	0.058	30% Bioavailability (F30%):	0.298
50% Bioavailability (F50%):	0.967

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.882	MRP1:	0.318
Plasma Protein Binding (PPB):	93.591%	Volume Distribution (VD):	0.671
Fu:	6.874% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.836
BSEP inhibitor:	0.992

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	0.978	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.964
HLM stability:	0.027 ? 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):

15.644

Half-life (T1/2):

2.451

ADMET: Toxicity

hERG Blockers:	0.164	hERG Blockers (10um):	0.429
Human Hepatotoxicity (H-HT):	0.509	Drug-induced Liver Injury (DILI):	0.322
AMES Toxicity:	0.166	Rat Oral Acute Toxicity:	0.249
Maximum Recommended Daily Dose:	0.935	Skin Sensitization:	0.96
Carcinogencity:	0.73	Eye Corrosion:	0.047
Eye Irritation:	0.661	Respiratory Toxicity:	0.242
Drug-induced Neurotoxicity:	0.047	Ototoxicity:	0.756
Hematotoxicity:	0.026	Drug-induced Nephrotoxicity:	0.267
Genotoxicity:	0.004	RPMI-8226 Immunitoxicity:	0.112
A549 Cytotoxicity:	0.084	Hek293 Cytotoxicity:	0.605
BCF:	1.545 ? 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:	3.596 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.003 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.397 ? 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
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[17268112]
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[6893493]
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[6893493]
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO44306	Reineckia carnes	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO157	Convallaria majalis	Species	Asparagaceae	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 NPC539394 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	24219
0.1-0.2	23671
0.2-0.3	1751
0.3-0.4	150
0.4-0.5	46
0.5-0.6	13
0.6-0.7	8
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
0.7692	Intermediate Similarity	NPC481427
0.6351	Remote Similarity	NPC176406
0.6216	Remote Similarity	NPC228049
0.6098	Remote Similarity	NPC481424
0.6098	Remote Similarity	NPC481422
0.6098	Remote Similarity	NPC481423
0.6087	Remote Similarity	NPC248944
0.6087	Remote Similarity	NPC7479
0.6087	Remote Similarity	NPC257296
0.5946	Remote Similarity	NPC52585
0.5867	Remote Similarity	NPC68630
0.5844	Remote Similarity	NPC482599
0.5634	Remote Similarity	NPC227260
0.557	Remote Similarity	NPC473517
0.5366	Remote Similarity	NPC473570
0.5256	Remote Similarity	NPC177818
0.5172	Remote Similarity	NPC481425
0.5172	Remote Similarity	NPC481426
0.5165	Remote Similarity	NPC54619
0.5161	Remote Similarity	NPC125324
0.5135	Remote Similarity	NPC296734
0.5114	Remote Similarity	NPC13190

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC539394 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7561
0.1-0.2	1483
0.2-0.3	96
0.3-0.4	7
0.4-0.5	2
0.5-0.6	0
0.6-0.7	1
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
0.6087	Remote Similarity	NPD6928	Phase 2

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