NPASS Compound

Natural Product: NPC488911

Natural Product ID	NPC488911
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HHZQLQREDATOBM-CODXZCKSSA-M
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	23694214
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003569] Pregnane steroids [CHEMONTID:0001468] Gluco/mineralocorticoids, progestogins 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 67 69 0 0 0 0 0 0 0 0999 V2000 -3.8942 0.5245 1.5091 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6501 0.7869 0.0140 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8422 2.2309 -0.2087 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3478 2.6203 -1.5739 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4554 1.7444 -2.0279 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3714 2.2152 -2.7206 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4244 0.3455 -1.6375 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6031 -0.1055 -0.7050 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5550 -1.5381 -0.3006 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1909 -2.0451 -0.0433 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1594 -1.0720 0.3981 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8122 -1.6299 0.1352 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4073 -2.8120 0.9385 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1233 -2.8198 0.8275 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5032 -1.5242 0.1375 C 0 0 2 0 0 0 0 0 0 0 0 0 2.7893 -0.9805 0.6230 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9723 -0.7047 1.7934 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8848 -0.7667 -0.3461 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0534 -0.2536 0.2405 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1385 -0.0177 -0.5911 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0430 -0.2655 -1.8180 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4266 0.5210 -0.0949 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5748 1.9808 -0.4899 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4631 2.7703 0.0993 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5688 2.2644 0.8051 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3940 4.1361 -0.1318 O 0 0 0 0 0 1 0 0 0 0 0 0 0.3171 -0.6485 0.4757 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3615 -0.3418 1.9370 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1480 0.5273 -0.4123 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1670 1.1843 -0.1120 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2858 0.2407 -0.3356 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1480 1.7691 1.1359 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5297 -1.7692 -1.2312 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 Na 0 0 0 0 0 15 0 0 0 0 0 0 -4.7623 1.1952 1.7739 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2399 -0.4963 1.7035 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0597 0.8495 2.1276 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9294 2.7823 0.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6191 2.6003 0.5253 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5187 2.6650 -2.3075 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7538 3.6505 -1.4989 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1044 -0.3378 -2.1382 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2739 -1.7770 0.5108 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9605 -2.1037 -1.1936 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7779 -2.5925 -0.9377 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2714 -2.8506 0.7440 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2630 -0.9417 1.5013 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6499 -1.8871 -0.9465 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6513 -2.6292 2.0088 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8370 -3.7639 0.6158 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6023 -2.9333 1.8152 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4611 -3.6710 0.1895 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0893 -1.7064 -0.9188 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5682 -0.0247 -1.1192 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2355 -0.0489 -0.6242 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4719 0.4010 1.0046 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5487 2.3704 -0.1366 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4696 2.0850 -1.5958 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7985 -1.1903 2.4989 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6229 -0.1273 2.3934 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0119 0.5342 2.1147 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1943 0.1903 -1.4595 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9856 1.2487 -0.1821 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2747 2.0090 -0.8711 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3108 -0.0096 -1.4276 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5420 2.5602 1.1029 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0085 -2.6172 -1.4037 H 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 1 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 2 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 2 0 16 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 15 27 1 0 27 28 1 1 27 29 1 0 29 30 1 0 30 31 1 0 30 32 1 0 15 33 1 6 8 2 1 0 31 11 1 0 31 2 1 0 27 12 1 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 3 39 1 0 4 40 1 0 4 41 1 0 7 42 1 0 9 43 1 0 9 44 1 0 10 45 1 0 10 46 1 0 11 47 1 1 12 48 1 6 13 49 1 0 13 50 1 0 14 51 1 0 14 52 1 0 18 53 1 0 18 54 1 0 22 55 1 0 22 56 1 0 23 57 1 0 23 58 1 0 28 59 1 0 28 60 1 0 28 61 1 0 29 62 1 0 29 63 1 0 30 64 1 6 31 65 1 6 32 66 1 0 33 67 1 0 M CHG 2 26 -1 34 1 M END

Standard InCHIKey	HHZQLQREDATOBM-CODXZCKSSA-M
Standard InCHI	InChI=1S/C25H34O8.Na/c1-23-9-7-15(26)11-14(23)3-4-16-17-8-10-25(32,24(17,2)12-18(27)22(16)23)19(28)13-33-21(31)6-5-20(29)30;/h11,16-18,22,27,32H,3-10,12-13H2,1-2H3,(H,29,30);/q;+1/p-1/t16-,17-,18-,22+,23-,24-,25-;/m0./s1
SMILES	C[C@]12CCC(=O)C=C1CC[C@H]1[C@@H]3CC[C@](C(=O)COC(=O)CCC(=O)[O-])([C@@]3(C)C[C@@H]([C@H]21)O)O.[Na+]

Calculated Properties

Physi-Chem Properties

Molecular Weight:	461.22	Volume:	462.552 ? Van der Waals volume.
Dense:	0.997	LogP:	0.586 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.632 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.312 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	24.0
TPSA:	141.03 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.555	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.658	Fsp³:	0.76
MCE-18:	79.091 ? 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:	0.514	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.184	Promiscuous compounds:	0.994

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.663	MDCK Permeability:	-4.893
Pgp-inhibitor:	0.007	Pgp-substrate:	0.0
PAMPA:	0.87 ? 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):	0.207
20% Bioavailability (F20%):	0.999	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.691	MRP1:	0.174
Plasma Protein Binding (PPB):	96.731%	Volume Distribution (VD):	0.078
Fu:	3.58% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.839	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.001 ? 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):

2.9

Half-life (T1/2):

1.366

ADMET: Toxicity

hERG Blockers:	0.021	hERG Blockers (10um):	0.058
Human Hepatotoxicity (H-HT):	0.709	Drug-induced Liver Injury (DILI):	0.113
AMES Toxicity:	0.109	Rat Oral Acute Toxicity:	0.159
Maximum Recommended Daily Dose:	0.565	Skin Sensitization:	0.747
Carcinogencity:	0.809	Eye Corrosion:	0.0
Eye Irritation:	0.091	Respiratory Toxicity:	0.257
Drug-induced Neurotoxicity:	0.135	Ototoxicity:	0.865
Hematotoxicity:	0.553	Drug-induced Nephrotoxicity:	0.864
Genotoxicity:	0.994	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.002	Hek293 Cytotoxicity:	0.032
BCF:	0.535 ? 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:	3.268 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.918 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.146 ? 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
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/0031-9422(90)85349-K]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	DOI[10.1186/1471-2202-6-1]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10579865]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	leaf	n.a.	PMID[10716597]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10757718]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11374948]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11561442]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12579877]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1375626]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[1375626]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[1602302]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1602302]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[16864458]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	roots	n.a.	n.a.	PMID[16989518]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[17250858]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17265278]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[1823717]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	leaf	n.a.	PMID[1823717]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18554602]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	bark	n.a.	PMID[18996177]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	root	n.a.	n.a.	PMID[21486005]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[21486005]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21514608]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	dried roots	purchased from Sichuan Neautus Traditional Chinese Medicine Co. Ltd. (Chengdu, P.R. China)	n.a.	PMID[22148431]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	leaves	n.a.	n.a.	PMID[23268606]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23852638]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24549173]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24963543]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25237706]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	bark	n.a.	PMID[2534610]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[2816380]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	Leaves	n.a.	n.a.	PMID[29355322]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	Leaves	n.a.	n.a.	PMID[31556299]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7102323]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7304185]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8699928]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8722541]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	Database[Article]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13661	Tripterygium wilfordii	Species	Celastraceae	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
Cell line	1
Organism	1

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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	42400.0	nM	PMID[31556299]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	12589.25	nM	PMID[19734910]

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
-	Mus musculus	LOEL	=	30.0	mg/kg-day	ToxVal
-	Mus musculus	NOEL	=	30.0	mg/kg-day	ToxVal

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 NPC488911 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	16500
0.1-0.2	30379
0.2-0.3	2914
0.3-0.4	44
0.4-0.5	11
0.5-0.6	4
0.6-0.7	2
0.7-0.8	5
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8143	Intermediate Similarity	NPC482048
0.7286	Intermediate Similarity	NPC478926
0.6618	Remote Similarity	NPC18509
0.6618	Remote Similarity	NPC319582
0.5733	Remote Similarity	NPC44063
0.5286	Remote Similarity	NPC257176
0.5211	Remote Similarity	NPC328539
0.507	Remote Similarity	NPC144258

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488911 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5689
0.1-0.2	3216
0.2-0.3	150
0.3-0.4	54
0.4-0.5	22
0.5-0.6	7
0.6-0.7	4
0.7-0.8	5
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD6372	Approved
0.8154	Intermediate Similarity	NPD5739	Phase 4
0.8143	Intermediate Similarity	NPD6373	Phase 4
0.7465	Intermediate Similarity	NPD7320	Phase 4
0.7391	Intermediate Similarity	NPD4767	Approved
0.7286	Intermediate Similarity	NPD4768	Phase 4
0.7162	Intermediate Similarity	NPD6909	Phase 4
0.7067	Intermediate Similarity	NPD6908	Approved
0.6618	Remote Similarity	NPD4754	Approved
0.6618	Remote Similarity	NPD4755	Phase 4
0.6164	Remote Similarity	NPD5696	Phase 4
0.6	Remote Similarity	NPD6649	Approved
0.5733	Remote Similarity	NPD5697	Phase 4
0.5584	Remote Similarity	NPD6899	Phase 4
0.5325	Remote Similarity	NPD5695	Phase 3
0.5286	Remote Similarity	NPD3618	Phase 1
0.519	Remote Similarity	NPD4729	Approved
0.5125	Remote Similarity	NPD4730	Phase 4
0.5062	Remote Similarity	NPD5701	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