NPASS Compound

Natural Product: NPC289930

Natural Product ID	NPC289930
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YQGUGZPPHKJXNZ-LOYHVIPDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	53486320
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000254] Ethers [CHEMONTID:0002463] Diarylethers

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 88 94 0 0 0 0 0 0 0 0999 V2000 -3.9892 3.6252 2.1862 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4570 2.7179 1.2019 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.5740 3.1308 0.4415 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4354 1.8790 0.2096 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5570 0.7468 -0.2145 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2382 -0.3197 -0.8147 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5349 -1.4183 -1.2542 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1653 -1.4329 -1.0875 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4807 -0.3919 -0.4996 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1950 0.7271 -0.0506 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5101 1.8605 0.6092 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5234 2.5193 -0.3145 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1069 2.2485 0.0234 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2177 2.0566 -1.0098 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1094 1.7805 -0.7757 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5576 1.6945 0.5443 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6624 1.8887 1.5716 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6486 2.1615 1.3114 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8555 1.4233 0.8713 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7808 0.6617 0.2517 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9599 -0.6806 0.4312 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9341 -1.3946 -0.2363 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0415 -2.8251 0.0577 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7329 -3.2115 1.4706 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9040 -2.3173 2.2054 N 0 0 0 0 0 0 0 0 0 0 0 0 4.5860 -1.5809 3.2430 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1048 -1.4482 1.3505 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1658 -2.3654 0.5954 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7795 -2.0491 0.9886 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3199 -2.4791 2.2112 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9895 -2.2079 2.5970 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8141 -1.5108 1.7514 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3393 -1.0878 0.5326 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0504 -1.3575 0.1583 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1280 -0.3924 -0.3321 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7771 -0.7867 -1.1235 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6219 0.5825 -1.3330 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6496 1.2800 -0.6608 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4878 2.6371 -0.8612 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1500 3.6268 -0.1067 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4692 1.2072 -2.2285 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4791 0.5116 -2.9308 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4493 -2.5170 -1.5188 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8807 -2.7057 -2.7779 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1301 -2.5176 -1.8600 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5340 -2.5080 -2.0353 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7902 4.4083 2.3337 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9398 3.0857 3.1670 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0335 4.1213 1.9646 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3824 3.5567 -0.5390 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1420 3.8770 1.0375 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2522 2.0691 -0.5001 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8847 1.6389 1.1945 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3083 -0.3099 -0.9460 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9061 1.4051 1.4356 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6553 3.6159 -0.3973 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7095 2.1132 -1.3270 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5413 2.1190 -2.0451 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8085 1.6285 -1.5712 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0048 1.8237 2.5839 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3131 2.3133 2.1530 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0544 -3.2316 -0.2518 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3390 -3.3800 -0.6117 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7275 -3.2420 2.0056 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3317 -4.2379 1.5646 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8207 -1.2382 3.9761 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2167 -2.3247 3.7881 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1499 -0.7150 2.8950 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5500 -0.7610 2.0101 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2929 -2.1238 -0.5022 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4143 -3.4359 0.7793 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9507 -3.0309 2.8951 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3748 -2.5337 3.5521 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8632 -1.2886 2.0508 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2948 -1.0134 -0.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5423 -1.3289 -1.6543 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8861 3.5555 0.9703 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8069 4.6126 -0.4686 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2434 3.5777 -0.2703 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9349 1.1885 -3.6789 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0770 -0.3570 -3.5109 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2322 0.1563 -2.2127 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9131 -3.7828 -3.0402 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2674 -2.0435 -3.5636 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7858 -2.4587 -2.6805 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0813 -2.1910 -1.1389 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8036 -1.7687 -2.8421 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9113 -3.5307 -2.2996 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 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 33 35 1 0 22 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 39 40 1 0 37 41 1 0 41 42 1 0 8 43 1 0 43 44 1 0 7 45 1 0 45 46 1 0 11 2 1 0 18 13 1 0 38 20 1 0 10 5 1 0 27 21 1 0 34 29 2 0 35 9 1 0 1 47 1 0 1 48 1 0 1 49 1 0 3 50 1 0 3 51 1 0 4 52 1 0 4 53 1 0 6 54 1 0 11 55 1 1 12 56 1 0 12 57 1 0 14 58 1 0 15 59 1 0 17 60 1 0 18 61 1 0 23 62 1 0 23 63 1 0 24 64 1 0 24 65 1 0 26 66 1 0 26 67 1 0 26 68 1 0 27 69 1 1 28 70 1 0 28 71 1 0 30 72 1 0 31 73 1 0 32 74 1 0 34 75 1 0 36 76 1 0 40 77 1 0 40 78 1 0 40 79 1 0 42 80 1 0 42 81 1 0 42 82 1 0 44 83 1 0 44 84 1 0 44 85 1 0 46 86 1 0 46 87 1 0 46 88 1 0 M END

Standard InCHIKey	YQGUGZPPHKJXNZ-LOYHVIPDSA-N
Standard InCHI	InChI=1S/C38H42N2O6/c1-39-16-14-25-21-32(42-4)36(44-6)38-33(25)29(39)19-23-10-12-27(13-11-23)45-37-34-26(22-31(41-3)35(37)43-5)15-17-40(2)30(34)20-24-8-7-9-28(18-24)46-38/h7-13,18,21-22,29-30H,14-17,19-20H2,1-6H3/t29-,30-/m1/s1
SMILES	CN1CCc2cc(c(c3c2[C@H]1Cc1ccc(cc1)Oc1c2c(CCN(C)[C@@H]2Cc2cccc(c2)O3)cc(c1OC)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	622.3	Volume:	649.006 ? Van der Waals volume.
Dense:	0.959	LogP:	3.741 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.228 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.596 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	42.0
TPSA:	61.86 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	8.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.238	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.614	Fsp³:	0.368
MCE-18:	129.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.999	Fluc inhibitor:	0.124 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.714 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.932 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.247

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.646	MDCK Permeability:	-4.71
Pgp-inhibitor:	0.906	Pgp-substrate:	0.637
PAMPA:	0.0 ? 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%):	0.407	30% Bioavailability (F30%):	0.547
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.911	MRP1:	0.986
Plasma Protein Binding (PPB):	84.799%	Volume Distribution (VD):	0.268
Fu:	16.533% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.987
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.981	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.005
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.267
CYP2B6-substrate:	0.999	CYP2C8-inhibitor:	0.035
HLM stability:	0.665 ? 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):

8.895

Half-life (T1/2):

1.69

ADMET: Toxicity

hERG Blockers:	0.852	hERG Blockers (10um):	0.863
Human Hepatotoxicity (H-HT):	0.55	Drug-induced Liver Injury (DILI):	0.009
AMES Toxicity:	0.541	Rat Oral Acute Toxicity:	0.668
Maximum Recommended Daily Dose:	0.963	Skin Sensitization:	0.637
Carcinogencity:	0.738	Eye Corrosion:	0.0
Eye Irritation:	0.004	Respiratory Toxicity:	0.736
Drug-induced Neurotoxicity:	0.92	Ototoxicity:	0.477
Hematotoxicity:	0.093	Drug-induced Nephrotoxicity:	0.229
Genotoxicity:	0.287	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.217	Hek293 Cytotoxicity:	0.656
BCF:	2.587 ? 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:	4.722 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.24 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.807 ? 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
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	roots	n.a.	n.a.	PMID[20593839]
NPO14376	Stephania cephalantha	Species	Menispermaceae	Eukaryota	n.a.	stem	n.a.	PMID[21214233]
NPO14376	Stephania cephalantha	Species	Menispermaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21214233]
NPO31374	Stephania cepharantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32129063]
NPO24050	Stephania glabra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31374	Stephania cepharantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14376	Stephania cephalantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9266	Stephania delavayi	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26272	Heracleum wallichii	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23832	Cyclea sutchuenensis	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24050	Stephania glabra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO31374	Stephania cepharantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9266	Stephania delavayi	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14376	Stephania cephalantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26272	Heracleum wallichii	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24050	Stephania glabra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23832	Cyclea sutchuenensis	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24050	Stephania glabra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9266	Stephania delavayi	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23832	Cyclea sutchuenensis	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31374	Stephania cepharantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9266	Stephania delavayi	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23832	Cyclea sutchuenensis	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24050	Stephania glabra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13978	Cissampelos pareira	Species	Menispermaceae	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 NPC289930 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	31287
0.1-0.2	17571
0.2-0.3	746
0.3-0.4	121
0.4-0.5	58
0.5-0.6	50
0.6-0.7	16
0.7-0.8	1
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8727	High Similarity	NPC317439
0.7164	Intermediate Similarity	NPC76682
0.7164	Intermediate Similarity	NPC10908
0.7164	Intermediate Similarity	NPC63646
0.7164	Intermediate Similarity	NPC317145
0.7164	Intermediate Similarity	NPC198498
0.7164	Intermediate Similarity	NPC115284
0.7059	Intermediate Similarity	NPC276890
0.6957	Remote Similarity	NPC227060
0.6901	Remote Similarity	NPC480587
0.6622	Remote Similarity	NPC223690
0.6622	Remote Similarity	NPC9532
0.64	Remote Similarity	NPC185639
0.64	Remote Similarity	NPC251735
0.64	Remote Similarity	NPC49075
0.64	Remote Similarity	NPC599951
0.6338	Remote Similarity	NPC41376
0.6216	Remote Similarity	NPC73492
0.6216	Remote Similarity	NPC299990
0.6164	Remote Similarity	NPC12424
0.6164	Remote Similarity	NPC129518
0.6164	Remote Similarity	NPC251580
0.6061	Remote Similarity	NPC247639
0.6061	Remote Similarity	NPC25084
0.5976	Remote Similarity	NPC480586
0.5875	Remote Similarity	NPC475479
0.5875	Remote Similarity	NPC323537
0.5867	Remote Similarity	NPC603853
0.5854	Remote Similarity	NPC10871
0.5844	Remote Similarity	NPC239824
0.5821	Remote Similarity	NPC104196
0.5802	Remote Similarity	NPC485712
0.5696	Remote Similarity	NPC229373
0.5641	Remote Similarity	NPC311973
0.561	Remote Similarity	NPC24260
0.5595	Remote Similarity	NPC480590
0.5584	Remote Similarity	NPC290582
0.5584	Remote Similarity	NPC217748
0.5584	Remote Similarity	NPC182052
0.5584	Remote Similarity	NPC271013
0.5584	Remote Similarity	NPC42663
0.5584	Remote Similarity	NPC15414
0.557	Remote Similarity	NPC116465
0.5513	Remote Similarity	NPC279228
0.55	Remote Similarity	NPC274716
0.55	Remote Similarity	NPC167116
0.55	Remote Similarity	NPC609821
0.5455	Remote Similarity	NPC234318
0.5422	Remote Similarity	NPC8836
0.5417	Remote Similarity	NPC317272
0.5417	Remote Similarity	NPC268503
0.5395	Remote Similarity	NPC603603
0.5375	Remote Similarity	NPC254441
0.5366	Remote Similarity	NPC16357
0.5366	Remote Similarity	NPC302245
0.5301	Remote Similarity	NPC212237
0.525	Remote Similarity	NPC112248
0.5238	Remote Similarity	NPC314682
0.5238	Remote Similarity	NPC249996
0.5238	Remote Similarity	NPC611658
0.5172	Remote Similarity	NPC281581
0.5169	Remote Similarity	NPC475597
0.5156	Remote Similarity	NPC213206
0.5156	Remote Similarity	NPC188163
0.5156	Remote Similarity	NPC328750
0.5128	Remote Similarity	NPC240841
0.5114	Remote Similarity	NPC485711
0.506	Remote Similarity	NPC181796
0.506	Remote Similarity	NPC290005
0.506	Remote Similarity	NPC54654
0.506	Remote Similarity	NPC7715
0.506	Remote Similarity	NPC328155
0.506	Remote Similarity	NPC222661
0.506	Remote Similarity	NPC285931

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC289930 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4167
0.1-0.2	4763
0.2-0.3	201
0.3-0.4	14
0.4-0.5	1
0.5-0.6	2
0.6-0.7	1
0.7-0.8	1
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
0.7164	Intermediate Similarity	NPD8099	Discontinued
0.6528	Remote Similarity	NPD8156	Discontinued
0.5789	Remote Similarity	NPD8095	Phase 1
0.5156	Remote Similarity	NPD4664	Clinical (unspecified phase)

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