NPASS Compound

Natural Product: NPC476380

Natural Product ID	NPC476380
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cistantubuloside B1
IUPAC Name	[(2R,3R,4R,5R,6R)-6-[2-(3,4-dihydroxyphenyl)ethoxy]-5-hydroxy-2-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]-4-[[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]methoxy]oxan-3-yl] (E)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms	Cistantubuloside B1
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL590344
PubChem CID	46228752
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0003002] Hydroxycinnamic acid esters [CHEMONTID:0000465] Coumaric acid esters

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 103107 0 0 0 0 0 0 0 0999 V2000 2.6491 0.9642 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 1.8121 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 2.3251 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8296 3.8023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2391 3.2893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3882 4.2535 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1277 5.7307 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7181 6.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 5.2795 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 4.7665 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0105 5.7307 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2709 7.2079 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3991 5.2176 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5481 6.1818 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9577 5.6688 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2181 4.1916 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6277 3.6786 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7768 4.6427 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5163 6.1199 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1067 6.6330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1863 4.1297 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 7.2079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 8.1721 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6805 9.6493 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1805 9.6493 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4305 10.9483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1805 12.2474 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6805 12.2474 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4305 10.9483 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0900 12.7604 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4996 13.2734 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4410 13.7246 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7186 11.9125 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2291 9.1362 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7977 4.7665 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0582 6.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3186 7.7209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5791 9.1981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4300 10.1623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6905 11.6395 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1001 12.1525 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2491 11.1884 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9887 9.7112 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3605 13.6298 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5415 12.6037 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3882 2.3251 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 -0.9642 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 -2.7762 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1595 -1.8121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 1.9284 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6132 -0.1849 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6849 2.1132 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4895 -2.7762 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 -1.8121 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1686 0.4341 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 2.7762 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4785 3.1486 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5215 1.1018 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3407 3.9852 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4891 1.9902 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2909 3.0555 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4681 7.5427 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6663 6.4775 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6595 3.7404 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2877 7.6590 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0691 3.2274 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8882 2.2013 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6653 7.0841 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8463 8.1102 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3354 5.0939 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6661 8.2309 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4720 6.1849 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1420 9.3119 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4410 8.1721 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8275 10.1314 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2291 12.7604 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 13.7246 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5770 14.1699 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6031 11.3508 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7600 14.7506 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2919 14.6887 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1281 11.3995 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4871 9.9532 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6879 6.8539 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5354 5.9832 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8414 7.9814 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7959 7.4604 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0205 9.6493 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.6587 11.7014 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1377 8.7470 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7701 14.1428 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8019 14.0809 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8497 2.6625 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0586 -0.4512 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6386 -3.7404 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4200 -3.2893 0.0000 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 1 0 6 7 1 0 6 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 2 0 17 19 1 0 19 20 2 3 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 24 27 1 0 14 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 33 38 1 0 32 39 1 0 31 40 1 0 12 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 44 45 2 0 45 46 1 0 46 47 2 0 47 48 1 0 48 49 2 0 47 50 1 0 46 51 1 0 11 52 1 0 5 53 1 0 4 54 1 0 3 55 1 0 7 2 1 0 15 10 1 0 26 21 1 0 35 30 1 0 49 44 1 0 1 56 1 0 1 57 1 0 1 58 1 0 2 59 1 0 3 60 1 0 4 61 1 0 5 62 1 0 6 63 1 0 8 64 1 0 8 65 1 0 10 66 1 0 11 67 1 0 12 68 1 0 14 69 1 0 15 70 1 0 19 71 1 0 20 72 1 0 22 73 1 0 23 74 1 0 25 75 1 0 26 76 1 0 27 77 1 0 28 78 1 0 28 79 1 0 30 80 1 0 31 81 1 0 32 82 1 0 33 83 1 0 34 84 1 0 36 85 1 0 36 86 1 0 37 87 1 0 38 88 1 0 39 89 1 0 40 90 1 0 42 91 1 0 42 92 1 0 43 93 1 0 43 94 1 0 45 95 1 0 48 96 1 0 49 97 1 0 50 98 1 0 51 99 1 0 52100 1 0 53101 1 0 54102 1 0 55103 1 0 M END

Standard InCHIKey	LYUXGWUGUULZMY-VQBKRXHASA-N
Standard InCHI	InChI=1S/C36H48O19/c1-16-26(42)29(45)28(44)23(52-16)14-50-34-32(48)36(49-11-10-18-4-8-20(39)21(40)12-18)54-24(15-51-35-31(47)30(46)27(43)22(13-37)53-35)33(34)55-25(41)9-5-17-2-6-19(38)7-3-17/h2-9,12,16,22-24,26-40,42-48H,10-11,13-15H2,1H3/b9-5+/t16-,22+,23-,24+,26-,27+,28-,29+,30-,31+,32+,33+,34+,35+,36+/m0/s1
SMILES	CC1C(C(C(C(O1)COC2C(C(OC(C2OC(=O)C=CC3=CC=C(C=C3)O)COC4C(C(C(C(O4)CO)O)O)O)OCCC5=CC(=C(C=C5)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	784.28	Volume:	734.352 ? Van der Waals volume.
Dense:	1.068	LogP:	-0.767 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.012 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.551 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	32.0
TPSA:	304.21 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	11.0	Rings:	5.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.052	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.361	Fsp³:	0.583
MCE-18:	126.947 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.33	Fluc inhibitor:	0.481 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.12 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.726 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.406	Promiscuous compounds:	0.533

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.422	MDCK Permeability:	-5.1
Pgp-inhibitor:	0.0	Pgp-substrate:	0.991
PAMPA:	1.0 ? 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):	1.0
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.947
Plasma Protein Binding (PPB):	60.792%	Volume Distribution (VD):	-0.368
Fu:	36.497% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.66	BCRP inhibitor:	0.033
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.896	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
HLM stability:	0.013 ? 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):

1.654

Half-life (T1/2):

3.675

ADMET: Toxicity

hERG Blockers:	0.072	hERG Blockers (10um):	0.75
Human Hepatotoxicity (H-HT):	0.289	Drug-induced Liver Injury (DILI):	0.283
AMES Toxicity:	0.872	Rat Oral Acute Toxicity:	0.144
Maximum Recommended Daily Dose:	0.258	Skin Sensitization:	0.955
Carcinogencity:	0.015	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.001
Drug-induced Neurotoxicity:	0.16	Ototoxicity:	0.998
Hematotoxicity:	0.003	Drug-induced Nephrotoxicity:	0.023
Genotoxicity:	0.149	RPMI-8226 Immunitoxicity:	0.036
A549 Cytotoxicity:	0.418	Hek293 Cytotoxicity:	0.932
BCF:	0.542 ? 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:	2.95 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.033 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.986 ? 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
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	fresh stems	n.a.	n.a.	PMID[20159656]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	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
Inhibition	8
IC50	1

Activity Type	# Activity
Cell line	9

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
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	3.1	%	PMID[22206869]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	10.3	%	DOI[10.6019/CHEMBL1201861]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	18.5	%	PMID[25127165]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	31.2	%	PMID[12828469]
NPT1460	Cell line	L929	Mus musculus	Inhibition	=	-14.7	%	PMID[19105653]
NPT1460	Cell line	L929	Mus musculus	Inhibition	=	31.0	%	PubChem BioAssay data set
NPT1460	Cell line	L929	Mus musculus	Inhibition	=	32.8	%	PMID[18407692]
NPT1460	Cell line	L929	Mus musculus	Inhibition	=	122.7	%	PMID[18490506]
NPT1460	Cell line	L929	Mus musculus	IC50	=	21.4	ug.mL-1	PMID[18183025]

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 NPC476380 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	15594
0.1-0.2	29267
0.2-0.3	4361
0.3-0.4	495
0.4-0.5	79
0.5-0.6	33
0.6-0.7	19
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9326	High Similarity	NPC476381
0.9318	High Similarity	NPC476384
0.8454	Intermediate Similarity	NPC476386
0.8298	Intermediate Similarity	NPC476378
0.7708	Intermediate Similarity	NPC476375
0.7634	Intermediate Similarity	NPC298257
0.7634	Intermediate Similarity	NPC175214
0.7188	Intermediate Similarity	NPC119537
0.7097	Intermediate Similarity	NPC76406
0.6947	Remote Similarity	NPC476376
0.6735	Remote Similarity	NPC205864
0.6735	Remote Similarity	NPC247032
0.6731	Remote Similarity	NPC64195
0.6569	Remote Similarity	NPC476382
0.6495	Remote Similarity	NPC611289
0.6476	Remote Similarity	NPC470933
0.6471	Remote Similarity	NPC300894
0.6471	Remote Similarity	NPC23845
0.6211	Remote Similarity	NPC81515
0.6195	Remote Similarity	NPC257970
0.6186	Remote Similarity	NPC472350
0.6186	Remote Similarity	NPC197316
0.6186	Remote Similarity	NPC89105
0.6162	Remote Similarity	NPC476377
0.6162	Remote Similarity	NPC476383
0.6146	Remote Similarity	NPC46137
0.6038	Remote Similarity	NPC106818
0.6	Remote Similarity	NPC259347
0.5978	Remote Similarity	NPC34293
0.5865	Remote Similarity	NPC112
0.5825	Remote Similarity	NPC269141
0.5818	Remote Similarity	NPC87403
0.5804	Remote Similarity	NPC229505
0.5784	Remote Similarity	NPC263829
0.5784	Remote Similarity	NPC47471
0.5776	Remote Similarity	NPC470927
0.5758	Remote Similarity	NPC205195
0.5728	Remote Similarity	NPC476385
0.5714	Remote Similarity	NPC260425
0.566	Remote Similarity	NPC100998
0.5619	Remote Similarity	NPC252292
0.5463	Remote Similarity	NPC96795
0.5463	Remote Similarity	NPC264632
0.5446	Remote Similarity	NPC64141
0.5426	Remote Similarity	NPC287597
0.54	Remote Similarity	NPC235294
0.5398	Remote Similarity	NPC470934
0.5392	Remote Similarity	NPC483705
0.5376	Remote Similarity	NPC288416
0.5294	Remote Similarity	NPC483706
0.5268	Remote Similarity	NPC196063
0.5268	Remote Similarity	NPC604195
0.5263	Remote Similarity	NPC886
0.5229	Remote Similarity	NPC34927
0.5192	Remote Similarity	NPC68092
0.5158	Remote Similarity	NPC477294
0.5116	Remote Similarity	NPC266045
0.5093	Remote Similarity	NPC34587
0.5086	Remote Similarity	NPC306890
0.5045	Remote Similarity	NPC610636
0.5043	Remote Similarity	NPC94871

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476380 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5590
0.1-0.2	3501
0.2-0.3	58
0.3-0.4	0
0.4-0.5	0
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
0.6186	Remote Similarity	NPD7266	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