NPASS Compound

Natural Product: NPC38423

Natural Product ID	NPC38423
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KONRSXDGNUZJIJ-QXRHLGINSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	86295613
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002875] Tigliane and ingenane diterpenoids

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 94 97 0 0 0 0 0 0 0 0999 V2000 12.3446 -0.6656 -1.7806 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2199 -1.2066 -0.9573 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8716 -0.7584 -1.4510 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7377 0.7498 -1.4254 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3823 1.1642 -1.9249 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2590 0.5818 -1.0751 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4118 1.0683 0.3311 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3557 0.5188 1.2224 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9919 0.9418 0.7274 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9898 0.3468 1.6974 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5456 0.6983 1.3173 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2348 0.1768 -0.0386 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8510 0.4580 -0.4909 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1417 -0.1897 0.3734 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2224 -0.9313 1.3093 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5038 0.0444 0.1209 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4493 -0.5611 0.9256 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4461 0.3557 1.5404 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5790 0.3759 0.8279 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4231 -0.5164 -0.3083 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3043 0.2944 -1.5355 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5546 1.5709 -1.4081 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7355 0.6409 -1.9363 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6631 0.9868 -0.8827 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.3251 0.0993 0.0002 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.8367 -1.3075 0.2273 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.2669 -1.4560 1.6341 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0662 -1.9489 2.0075 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8869 -1.9976 3.4900 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0094 -1.5189 4.1169 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9726 -2.4319 1.1351 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4068 -1.4550 0.1376 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7433 -2.1485 -0.8620 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2858 -3.6586 0.5413 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6166 -1.4120 -0.6130 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4979 -2.1542 -1.5198 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1159 0.4992 -1.1532 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3574 -0.3608 -2.3498 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1717 1.6072 -0.9981 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1275 1.1228 2.7945 C 0 0 0 0 0 0 0 0 0 0 0 0 12.9879 -1.5304 -2.1173 H 0 0 0 0 0 0 0 0 0 0 0 0 11.9811 -0.1224 -2.6656 H 0 0 0 0 0 0 0 0 0 0 0 0 12.9666 0.0410 -1.1620 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2114 -2.3228 -0.9725 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3707 -0.9104 0.1084 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7510 -1.1319 -2.4838 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0858 -1.2378 -0.8344 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4787 1.1605 -2.1633 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0224 1.1640 -0.4544 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2766 0.7991 -2.9483 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2807 2.2565 -1.8737 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2013 -0.5149 -1.1475 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3217 0.9964 -1.5291 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4609 2.1738 0.3798 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4073 0.7077 0.6962 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3561 -0.5933 1.2331 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4504 0.9120 2.2670 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9091 2.0301 0.6997 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8650 0.4964 -0.2833 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1517 0.8005 2.6953 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0805 -0.7508 1.7516 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4998 1.8124 1.3284 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9339 0.2509 2.1153 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4704 -0.9126 -0.0619 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9306 0.6429 -0.7762 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6408 1.5646 -0.5727 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7542 0.0793 -1.5353 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9407 -1.1730 1.6987 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3848 1.0121 1.1871 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8279 -0.3148 -2.3259 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5524 1.5401 -1.9292 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4472 1.9248 -0.3570 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1022 2.3821 -1.9289 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0639 -0.1911 -2.6228 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6253 1.5140 -2.6461 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5870 2.0785 -0.5708 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7168 0.5235 0.9752 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5733 -2.0840 0.0286 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9159 -1.1220 2.4127 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7682 -3.0899 3.7245 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9930 -1.4354 3.7847 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9464 -1.6503 5.0969 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1217 -2.6962 1.8397 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7698 -1.9585 -0.7464 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5045 -4.2506 0.4848 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9644 0.1127 -3.2969 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4550 -0.4227 -2.4966 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0233 -1.4106 -2.2419 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1260 1.1439 -0.6932 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7743 2.3342 -0.2611 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2432 2.1358 -1.9705 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6876 2.0966 2.5689 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1073 1.3419 3.3121 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5552 0.5147 3.5136 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 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 2 0 14 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 20 19 1 1 20 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 1 0 28 31 1 0 31 32 1 0 32 33 1 6 31 34 1 0 26 35 1 0 35 36 2 0 25 37 1 0 37 38 1 0 37 39 1 0 18 40 1 0 32 17 1 0 35 20 1 0 32 20 1 0 37 24 1 0 1 41 1 0 1 42 1 0 1 43 1 0 2 44 1 0 2 45 1 0 3 46 1 0 3 47 1 0 4 48 1 0 4 49 1 0 5 50 1 0 5 51 1 0 6 52 1 0 6 53 1 0 7 54 1 0 7 55 1 0 8 56 1 0 8 57 1 0 9 58 1 0 9 59 1 0 10 60 1 0 10 61 1 0 11 62 1 0 11 63 1 0 12 64 1 0 12 65 1 0 13 66 1 0 13 67 1 0 17 68 1 1 19 69 1 0 21 70 1 6 22 71 1 0 22 72 1 0 22 73 1 0 23 74 1 0 23 75 1 0 24 76 1 1 25 77 1 1 26 78 1 6 27 79 1 0 29 80 1 0 29 81 1 0 30 82 1 0 31 83 1 1 33 84 1 0 34 85 1 0 38 86 1 0 38 87 1 0 38 88 1 0 39 89 1 0 39 90 1 0 39 91 1 0 40 92 1 0 40 93 1 0 40 94 1 0 M END

Standard InCHIKey	KONRSXDGNUZJIJ-QXRHLGINSA-N
Standard InCHI	InChI=1S/C34H54O6/c1-6-7-8-9-10-11-12-13-14-15-16-17-27(36)40-31-22(2)20-33-23(3)18-26-28(32(26,4)5)25(30(33)38)19-24(21-35)29(37)34(31,33)39/h19-20,23,25-26,28-29,31,35,37,39H,6-18,21H2,1-5H3/t23-,25+,26-,28+,29-,31+,33+,34+/m1/s1
SMILES	CCCCCCCCCCCCCC(=O)O[C@H]1C(=C[C@]23[C@H](C)C[C@@H]4[C@H]([C@H](C=C(CO)[C@H]([C@]13O)O)C2=O)C4(C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	558.39	Volume:	604.59 ? Van der Waals volume.
Dense:	0.924	LogP:	6.251 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.652 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.399 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	20.0
TPSA:	104.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.136	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.942	Fsp³:	0.824
MCE-18:	103.0 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.398	Fluc inhibitor:	0.016 ? 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:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.208	Promiscuous compounds:	0.533

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.118	MDCK Permeability:	-4.671
Pgp-inhibitor:	0.002	Pgp-substrate:	0.449
PAMPA:	0.008 ? 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):	0.72
20% Bioavailability (F20%):	0.991	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.723
Plasma Protein Binding (PPB):	97.941%	Volume Distribution (VD):	0.704
Fu:	3.422% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.955
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.121
BSEP inhibitor:	0.801

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.041
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.034
CYP2C9-inhibitor:	0.007	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	0.992
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	0.053 ? 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):

5.065

Half-life (T1/2):

1.079

ADMET: Toxicity

hERG Blockers:	0.16	hERG Blockers (10um):	0.522
Human Hepatotoxicity (H-HT):	0.652	Drug-induced Liver Injury (DILI):	0.164
AMES Toxicity:	0.168	Rat Oral Acute Toxicity:	0.165
Maximum Recommended Daily Dose:	0.299	Skin Sensitization:	0.995
Carcinogencity:	0.653	Eye Corrosion:	0.02
Eye Irritation:	0.836	Respiratory Toxicity:	0.668
Drug-induced Neurotoxicity:	0.01	Ototoxicity:	0.592
Hematotoxicity:	0.241	Drug-induced Nephrotoxicity:	0.605
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.071
A549 Cytotoxicity:	0.353	Hek293 Cytotoxicity:	0.268
BCF:	1.863 ? 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:	5.546 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.985 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.661 ? 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
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	roots	n.a.	n.a.	PMID[24660966]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[29148766]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31184480]
NPO5402	Hypogymnia billardieri	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8081	Crataegus flava	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1891	Chorilaena quercifolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12190	Carduus acanthoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16779.1	Amaranthus hybridus subsp. cruentus	Subspecies	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12190	Carduus acanthoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16779.1	Amaranthus hybridus subsp. cruentus	Subspecies	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5402	Hypogymnia billardieri	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12190	Carduus acanthoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8081	Crataegus flava	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1891	Chorilaena quercifolia	Species	Rutaceae	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	1
Ratio CC50/IC50	1
CC50	1

Activity Type	# Activity
Cell line	1
Organism	1
Others	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
NPT25	Cell line	MT4	Homo sapiens	CC50	=	26300.0	nM	PMID[31184480]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	IC50	=	2.3	nM	PMID[31184480]
NPT2	Others	Unspecified	n.a.	Ratio CC50/IC50	=	11307.7	n.a.	PMID[31184480]

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 NPC38423 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	16691
0.1-0.2	29518
0.2-0.3	3520
0.3-0.4	86
0.4-0.5	12
0.5-0.6	16
0.6-0.7	5
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	2
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC308191
0.9818	High Similarity	NPC607683
0.9167	High Similarity	NPC482240
0.9167	High Similarity	NPC482239
0.7869	Intermediate Similarity	NPC257240
0.7463	Intermediate Similarity	NPC46269
0.7463	Intermediate Similarity	NPC106395
0.746	Intermediate Similarity	NPC267734
0.746	Intermediate Similarity	NPC482241
0.6562	Remote Similarity	NPC600642
0.6462	Remote Similarity	NPC482234
0.6462	Remote Similarity	NPC303053
0.6438	Remote Similarity	NPC607157
0.6197	Remote Similarity	NPC47951
0.5789	Remote Similarity	NPC67290
0.5789	Remote Similarity	NPC133677
0.5658	Remote Similarity	NPC482242
0.5658	Remote Similarity	NPC482243
0.56	Remote Similarity	NPC138757
0.5556	Remote Similarity	NPC261341
0.5405	Remote Similarity	NPC609657
0.5395	Remote Similarity	NPC138303
0.5278	Remote Similarity	NPC473488
0.5278	Remote Similarity	NPC92898
0.5278	Remote Similarity	NPC31883
0.5278	Remote Similarity	NPC179891
0.527	Remote Similarity	NPC482235
0.527	Remote Similarity	NPC479252
0.5063	Remote Similarity	NPC134131
0.5063	Remote Similarity	NPC25043

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC38423 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6395
0.1-0.2	2675
0.2-0.3	75
0.3-0.4	4
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
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
0.7869	Intermediate Similarity	NPD6371	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